预约演示
更新于：2026-09-02
Gemcitabine Hydrochloride
盐酸吉西他滨
更新于：2026-09-02
概要
基本信息
药物类型 小分子化药 |
别名 Gemcitabine hydrochloride (JAN/USP)、Gemcitabine Hydrochloride for jnjection、Gemcitabine Hydrochlride + [22] |
作用方式 抑制剂 |
作用机制 DNA抑制剂(DNA抑制剂)、RNR抑制剂(核糖核苷酸还原酶复合体抑制剂) |
在研适应症 |
原研机构 |
权益机构- |
最高研发阶段批准上市 |
最高研发阶段(中国)批准上市 |
特殊审评孤儿药 (美国)、孤儿药 (日本)、优先审评 (美国)、突破性疗法 (美国) |
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结构/序列
分子式C9H12ClF2N3O4 |
InChIKeyOKKDEIYWILRZIA-OSZBKLCCSA-N |
CAS号122111-03-9 |
关联
2,809
项与 盐酸吉西他滨 相关的临床试验JPRN-UMIN000006999
Phase II randomized trail of Gemcitabine and Irinotecan in Patients with Platinum Refractory and Resistant Mullerian carcinoma (tailored dose vs optimal dose chemotherapy)
开始日期2046-12-31 |
申办/合作机构- |
NCT06592664
A Phase 1b/2a, Double-blind, Placebo-controlled, Three Arm, Randomized Study Evaluating a Single Intravenous Push Followed by a Continuous Infusion of Certepetide Over 4 Hours When Added to Standard of Care (SoC) Versus Two Intravenous Pushes of Certepetide When Added to SoC, Versus SoC Alone in Subjects With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (FORTIFIDE)
The goal of this clinical trial is to test a new drug plus standard treatment compared with standard treatment alone in people with metastatic pancreatic ductal adenocarcinoma.
The main questions it aims to answer are:
* is the new drug plus standard treatment safe and tolerable
* is the new drug plus standard treatment more effective than standard treatment
Participants will:
* Visit the clinic three times every 28 days for treatment and tests
* Have CT or MRI scans every 8 weeks while on treatment
The main questions it aims to answer are:
* is the new drug plus standard treatment safe and tolerable
* is the new drug plus standard treatment more effective than standard treatment
Participants will:
* Visit the clinic three times every 28 days for treatment and tests
* Have CT or MRI scans every 8 weeks while on treatment
开始日期2030-01-01 |
申办/合作机构 |
NCT07639528
Phase II, Open Label, Non-Randomized, Study of Optimal Preoperative Therapy for Intrahepatic Cholangiocarcinoma (OPTIC)
This phase II trial tests the safety and effectiveness of preoperative immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine with or without futibatinib targeted therapy in treating patients with intrahepatic cholangiocarcinoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine and/or targeted therapy with futibatinib before surgery may make the tumor smaller for resection and may help prevent the cancer from coming back. Patients whose molecular profiling test result show a genetic change called FGFR2 fusion, rearrangement, or activating mutation, receive immunotherapy, chemotherapy and targeted therapy while patients without a FGFR2 fusion, rearrangement, or activating mutation just receive immunotherapy and chemotherapy. Giving targeted therapy based on molecular profile test results prior to attempted resection for patients with intrahepatic cholangiocarcinoma that has a risk for either not being able to be removed or for coming back after it has been removed may help improve treatment outcomes in patients with resectable intrahepatic cholangiocarcinoma.
开始日期2027-12-10 |
申办/合作机构 |
100 项与 盐酸吉西他滨 相关的临床结果
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100 项与 盐酸吉西他滨 相关的转化医学
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100 项与 盐酸吉西他滨 相关的专利（医药）
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15,302
项与 盐酸吉西他滨 相关的文献（医药）2026-12-31·JOURNAL OF MEDICAL ECONOMICS
Budget impact model of nadofaragene firadenovec for the treatment of high-risk non-muscle-invasive bladder cancer that is unresponsive to Bacillus Calmette-Guérin immunotherapy
Article
作者: Ye, Dongni ; Yang, Min ; Chai, Xinglei ; Moradi, Ashton ; Zhao, Angela ; Lotan, Yair
AIMS:
To estimate the budget impact of adopting nadofaragene firadenovec for the treatment of adults with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors (CIS ± Ta/T1) from a US third-party payer's perspective.
METHODS:
A budget impact model was developed to compare total healthcare costs under two scenarios: (1) with nadofaragene firadenovec included in the treatment mix, and (2) without it. The model simulated a hypothetical US health plan covering one million members over a 3-year time horizon. Costs assessed included drug acquisition and administration, surveillance and disease management, cystectomy, and treatment-related adverse events (AEs). Base-case inputs were informed by trial data, published literature, and real-world evidence. Scenario analyses explored alternative population definitions, epidemiology and clinical inputs; one-way sensitivity analyses tested parameter uncertainty.
RESULTS:
In the base-case, the estimated per-member-per-month (PMPM) budget impact of adopting nadofaragene firadenovec ranged from $0.0010 in Year 1 to $0.0084 in Year 3. Increased drug and administration costs were partially offset by cost savings from reduced disease progression, fewer cystectomies, and lower AE rates. Scenario analyses demonstrated that even examining a broader population including papillary disease-only patients, the budget impact remained modest ($0.0064-$0.0548 PMPM from Years 1-3). Sensitivity analyses confirmed that results were most influenced by uptake rate, drug cost, and target population size.
LIMITATIONS:
Key limitations include reliance on projected market shares for nadofaragene firadenovec, omission of recently approved treatments (nogapendekin alfa inbakicept-pmln and TAR-200) due to the lack of publicly available market share data, and assumptions to derive clinical outcomes for certain treatments due to lack of reported data.
CONCLUSIONS:
Despite its higher acquisition cost, the inclusion of nadofaragene firadenovec resulted in a minimal budget impact as bladder-sparing option for patients with BCG-unresponsive NMIBC with CIS ± Ta/T1.
2026-09-01·Translational Oncology
Can manual gemcitabine instillation or tumor microenvironment-based selection enhance the efficacy of TAR-200 in bladder cancer?
Letter
作者: Chen, Lei ; Liang, Chaozhao
TAR-200, a novel intravesical drug delivery system, has demonstrated remarkable efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer, achieving a complete response rate of 82.4% in the phase IIb SunRISe-1 study. In this letter, we propose two strategies to further optimize treatment outcomes. First, we suggest that a single manual gemcitabine instillation given concurrently with TAR-200 placement-without adding an extra procedure - could combine the high peak concentration of manual instillation with the sustained release profile of TAR-200, potentially enhancing antitumor activity. Second, we discuss the immunological mechanisms underlying BCG failure, particularly the development of an immunosuppressive tumor microenvironment characterized by upregulation of PD-L1 on tumor and immune cells. We hypothesize that assessing baseline or BCG-induced immunosuppressive status may help identify patients who would derive greater benefit from the addition of the PD-1 inhibitor cetrelimab to TAR-200. These considerations warrant further investigation to maximize therapeutic efficacy in this challenging patient population.
2026-08-01·UROLOGIC CLINICS OF NORTH AMERICA
Emerging Intravesical Therapies for Non–Muscle-Invasive Bladder Cancer
Review
作者: Bukavina, Laura ; Isali, Ilaha ; Wang, Betty ; Calaway, Adam
Non-Muscle-Invasive Bladder Cancer poses significant therapeutic challenges due to high recurrence and progression rates. While intravesical Bacillus Calmette-Guérin (BCG) has long been the standard, limitations in efficacy, global shortages, and patient-specific contraindications to radical cystectomy have fueled the development of novel bladder-sparing therapies. Recent advances include UGN-102 for low-grade/intermediate-risk disease and multiple FDA-approved agents-nadofaragene firadenovec, TAR-200, and nogapendekin alfa inbakicept-for BCG-unresponsive disease. Ongoing trials of TAR-210, cretostimogene, and other combination regimens promise to further expand options. Comparative studies and real-world evidence will be critical to define optimal sequencing, benchmark outcomes against radical cystectomy, and address quality-of-life considerations.
1,611
项与 盐酸吉西他滨 相关的新闻（医药）16 小时之前
·药学进展
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合成致死类药物的定量系统药理模型研究与应用进展 PPS
肖霞 1#，洪峻 1#，边康麒 2，赵宸 1*
（1. 南京医科大学药学院，江苏 南京 211166；2. 南京医科大学公共卫生学院，江苏 南京 211166）
赵宸
南京医科大学教授、博士生导师；获2023年度江苏青年五四奖章，2026年度全国新时代青年先锋奖，入选中国科协青年人才托举工程，江苏特聘医学专家，江苏卫生创新团队。美国华盛顿圣路易斯大学学士，约翰霍普金斯医学院博士，主要聚焦疾病-药物研究和临床试验中定量系统药理（QSP）建模与虚拟临床试验技术。长期致力于推动QSP前沿理念在国内的发展与应用，主编首部QSP领域中文专著，多次参与国家药品监督管理局药品审评中心（CDE）监管课题咨询及药物研发技术指导原则的编写工作。主持及承担国家自然科学基金、创新药物重大专项课题、省科技厅重点项目等10项基金，主导了30余个本土新药的QSP建模与应用项目 （涵盖创新小分子、大分子、细胞与基因治疗等领域），于国内外行业学术会议作QSP专题报告90余次，发表疾病-药物转化建模相关论文近30篇。曾获约翰霍普金斯医学院年度青年研究者奖、美国心脏协会杰出博士学者奖、中国生物医药产业链创新转化联合体 （CBIITA） U45影响力奖等多项荣誉。现任江苏省药学会模型引导药物研发专委会主任委员、CBIITA副秘书长、南京市青科协副会长等职务。
[摘要]合成致死作为一种精准靶向肿瘤细胞的治疗策略，在癌症治疗中已展现出巨大应用潜力。由于合成致死涉及多条修复通路，其药物靶点研究已从聚腺苷二磷酸核糖聚合酶（poly ADP-ribose polymerase，PARP）扩展至多个新靶点，相关药物已陆续进入关键临床研究阶段。尽管合成致死类药物具有显著的特异性抗癌疗效，但其临床研究仍面临易耐药、血液学毒性等挑战。综述详细总结了合成致死领域多个靶点的作用机制及相关定量系统药理学（quantitative systems pharmacology，QSP）模型研究进展，探讨 QSP 建模通过整合多尺度机制与实验数据，预测合成致死类药物的临床疗效及血液学毒性，从而在临床给药方案设计、剂量优化、联合疗法筛选等方面发挥指导作用，旨在从系统角度精准推动该类药物的临床转化，提升患者临床获益并降低安全性风险。
合成致死作为肿瘤治疗的重要策略，通过靶向DNA 损伤应答 （DNA damage response，DDR） 网络 ， 已 在 同 源 重 组 修 复 缺 陷 （homologous recombination deficiency，HRD） 阳性肿瘤的治疗中显示出显著疗效。然而，合成致死类药物的获得性耐药以及联合疗法中出现的骨髓抑制等毒性问题，仍是当前临床应用和新药研发中亟待解决的关键问题。近年来，基于定量系统药理学 （quantitative systems pharmacology，QSP） 建模方法，通过整合多尺度实验数据与定量模拟分析，为解析合成致死相互作用、优化给药策略及预测药物毒性谱提供了新思路。本综述系统梳理合成致死关键靶点的发现及相关药物研究进展，并重点探讨 QSP 模型在解析药物疗效机制、降低血液学毒性及指导临床转化方面的应用与挑战。
1
合成致死：从遗传现象到靶向治疗策略
1.1 合成致死概述
“合成致死”概念起源于 20 世纪初的果蝇遗传学研究。1922 年，Calvin Bridges 在黑腹果蝇杂交实验中首次观察到这一现象：当 2 条非同源染色体上的隐性突变单独存在时，果蝇个体均可正常存活；但当这 2 个突变同时纯合时，会导致果蝇在胚胎或成虫阶段死亡[1]。1946 年，Dobzhansky 将此类表型正式命名为“合成致死”，并将其定义为：仅当 2 个非等位基因同时发生遗传失活突变时才出现致死表型，任一基因单独突变均不影响个体存活[2]。20 世纪中叶，随着分子生物学和遗传学的快速发展，人们对基因突变在癌症发生中的作用有了更深入的了解。1997 年，Hartwell 和 Dulic 首次提出将合成致死效应应用于癌症治疗的设想[3]。此后，合成致死效应逐渐从模式生物研究拓展至人类疾病领域。2005 年，2 个英国研究团队同时发现了乳腺癌易感基因 （breast cancer susceptibility gene，BRCA） 1/2突变与聚腺苷二磷酸核糖聚合酶 （poly ADP-ribose polymerase，PARP）抑制剂之间存在合成致死关系，首次将 PARP 抑制剂引入 BRCA 突变肿瘤的治疗，开启了合成致死效应在精准抗癌领域的全新应用阶段[4–5]。
正常细胞在应对 DNA 损伤时，主要依赖多种相互关联的修复途径来维持基因组稳定性，其中包括以 BRCA1/2 为核心的同源重组修复 （homologous recombination，HR） 和由 PARP 介导的碱基切除修复 （base excision repair，BER）[6]。大量研究表明，乳腺癌和卵巢癌与 BRCA1/2 突变密切相关；此外，其他一些癌种的肿瘤细胞也存在 BRCA1/2 突变，并表 现 出 同 源 重 组 修 复 缺 陷 （homologous recom-bination deficiency，HRD）[7–9]。2014 年，美国食品药品监督管理局 （Food and Drug Admini-stration，FDA） 批准首个 PARP 抑制剂 olaparib 用于 BRCA突变型卵巢癌治疗[10]。这一里程碑事件标志着合成致死策略从基础研究成功走向临床应用，并开启了针对合成致死靶点的药物开发热潮。
1.2 DNA 损伤应答网络概述
DDR 网络是细胞维持基因组稳定性的关键机制，其可通过识别和修复 DNA 损伤来防止突变的积累[11–12]。DDR 网络涉及多种修复途径，可根据损伤类型和细胞周期阶段实现协同激活。双链断裂（double-strand break，DSB） 是最严重的 DNA 损伤类型之一，其主要通过 HR、非同源末端连接（non-homologous end joining，NHEJ） 和替代末端连接（alternative end joining， Alt-EJ） 3 种 途 径 进 行 修复[13]。HR 属于高保真修复机制，主要发生于 S 期和 G2期，依赖于姐妹染色单体作为修复模板，通过Rad51 蛋白复合体介导，可确保 DNA 序列的准确修复[14]。NHEJ 是 DSB 修复的主要途径，尤其在 G1期和非增殖细胞中起主导作用，主要通过直接连接断裂末端来修复 DSB，但可能会引入小的插入或缺失[15–16]。Alt-EJ 是一种与 NHEJ 相关的修复途径，但两者的作用机制有所不同，Alt-EJ 通常在 NHEJ途径受阻时发挥作用[16]。
单链断裂（single-strand break，SSB）通常由氧化应激或碱基损伤引起，主要通过 BER 和单链断裂修复（single-strand break repair，SSBR）2 种途径进行修复。BER 主要修复小的碱基损伤，如氧化损伤或脱嘌呤/脱嘧啶位点，该修复途径由多种酶参与，包括 DNA 糖基化酶、AP 内切酶和 DNA 聚合酶[17]。SSBR 主要修复由氧化应激或 DNA 损伤剂引起的SSB，其修复过程涉及多种蛋白复合体[18]。细胞周期检验点是 DDR 网络的重要组成部分，通过监测DNA 损伤状态来调节细胞周期进程，确保 DNA 损伤在细胞分裂前完成修复。DNA 发生损伤后，共济失 调 毛 细 血 管 扩 张 和 Rad3 相 关 激 酶 （ataxia telangiectasia and Rad3-related，ATR）会快速磷酸化细 胞 周 期 检 查 点 激 酶 1 （checkpoint kinase 1，CHK1） 的丝氨酸 317 和丝氨酸 345 位点，使其高度活化[19]。活化的 CHK1 会磷酸化多个下游靶点，导致细胞周期停滞，激活 DNA 修复途径，并在DNA 损伤严重时诱导细胞凋亡[20]。WEE1 G2检查点激酶 （WEE1 G2 checkpoint kinase，WEE1） 通路通过抑制细胞周期蛋白依赖性激酶的活性，阻止细胞进入有丝分裂，确保 DNA 损伤修复完成前细胞发生有丝分裂[21]。上述机制能够协同保障细胞在面对DNA 损伤时能有效修复，从而维持基因组稳定性和细胞正常生理功能。近年来，针对 WEE1、ATR 和CHK1 等关键 DDR 通路蛋白的抑制剂，已在部分癌症类型患者中显现出初步临床疗效，进一步证实了DDR 网络在癌症治疗领域的潜在应用价值[22]。
1.3 合成致死类药物临床治疗的挑战
尽管 HRD 作为合成致死重要通路已在肿瘤治疗中展现出巨大潜力，但目前仍存在诸多亟待解决的临床问题。首先，HRD 检测的异质性为精准诊断带来挑战。HRD 状态在不同肿瘤类型、不同患者之间以及同一患者的不同肿瘤部位均存在显著差异，这使得准确识别 HRD 阳性患者变得复杂[23–24]。例如，部分肿瘤初始检测为 HRD 阳性，但在治疗或肿瘤进展过程中可能转变为 HRD 阴性，这种动态变化增加了治疗决策的难度[25–26]。其次，合成致死类药物的耐药机制也日益受到关注。以 PARP 抑制剂为例，BRCA 功能重新激活、复制叉保护等机制均可能导致 PARP 抑制剂耐药，从而限制其长期疗效[27–28]。此外，贫血、中性粒细胞减少和血小板减少等血液学毒性是合成致死类药物治疗期间的常见不良事件[29–30]，这些安全风险可能会导致其停药，并降低与化疗或其他疗法联合使用的可能性。
2
合成致死类药物
2.1 PARP 抑制剂
PARP1/2 抑制剂通过与 PARP 结合形成 PARP-DNA 复合物，抑制 PARP 酶活性，从而阻断 DNA损伤修复，诱导细胞凋亡。该作用机制在具有 HRD特征的肿瘤细胞中表现出显著的合成致死效应。目前，已有多种 PARP1/2 抑制剂获批上市，包括olaparib、 niraparib、 rucaparib、 talazoparib 等[31–32]。Olaparib 是首个获批的 PARP 抑制剂，于 2014 年获FDA 批准用于 BRCA 突变型卵巢癌的治疗[10]。近期研究表明，PARP 抑制剂的临床应用可进一步扩展至非 BRCA 突变的癌症患者群体[33–35]。许多国内药企也已研发多款 PARP 抑制剂并已获批上市，例如pamiparib 和 fluzoparib 已被批准用于治疗卵巢癌，且在开展针对多种实体肿瘤的临床试验[36–37]。
PARP 捕获效能 （PARP-trapping potency） 是衡量 PARP 抑制剂将 PARP1/2 酶“锁”在 DNA 损伤位点、形成稳定 PARP-DNA 复合物并由此产生细胞毒性能力的定量指标[38]。该效能决定了 PARP 抑制剂将 PARP 转化为 DNA 毒性剂的效率，捕获效能越高，对 HRD 肿瘤细胞的合成致死效应越强[39]。例如，talazoparib 以高 PARP 捕获效能著称，每日用药剂量仅为 1 mg，而其他 PARP 捕获效能较低的PARP 抑制剂通常需要数百毫克剂量[40]。尽管高PARP 捕获效能能够增强药效，但也可能增加对骨髓等增殖组织的毒性，从而影响治疗安全性。
目前，已上市的多款非选择性 PARP1/2 抑制剂所引发的血液毒性问题，已成为临床应用中的重要难题。近年来，随着 PARP 抑制剂研发的持续推进，人们对 PARP1 和 PARP2 功能差异的认识也逐步深入 。 PARP1 在 DNA 损 伤 应 答 中 起 主 导 作 用 ，PARP2 的功能则相对次要，但 PARP2 在维持造血干细胞基因组完整性方面发挥至关重要的作用[41–42]。因 此 ， 近 年 来 高 选 择 性 PARP1 抑 制 剂 （如AZD5305） 已成为研发热点。临床前研究显示，AZD5305 是一种强效的选择性 PARP1 捕获剂，即使在高浓度条件下也未检测到 PARP2 的捕获作用；相比之下，olaparib、niraparib 和 talazoparib 在相似浓度下均会诱导 PARP1 和 PARP2 的捕获[43]，提示AZD5305 在临床毒性方面可能具有潜在优势。
2.2 ATR 抑制剂
ATR 信号通路的关键功能之一是调节 DNA 损伤后的 G2/M 细胞周期检查点。DNA 损伤发生后，ATR 通过磷酸化 CHK1，激活其激酶活性，进而调控细胞周期进程及 DNA 修复[44]。然而，当 ATR 被抑制时，基因组中会出现大量单链 DNA，导致复制叉大规模崩塌，进而引发细胞死亡，即所谓的“复制灾难”。同时，由于 ATR 信号通路被抑制，功能性检查点缺失，细胞会过早进入有丝分裂，导致DNA 损伤加剧，从而引发有丝分裂灾难 （mitotic catastrophe，MC）[45–46]。
值得注意的是，ATR 在多数肿瘤细胞中的功能比在正常细胞中更为关键。这主要是因为肿瘤细胞常携带已激活的致癌基因，这些基因破坏了正常的细胞周期调控机制，使得肿瘤细胞更加依赖 ATR 信号通路[47–48]。因此，ATR 作为一种极具潜力的抗肿瘤靶点，受到广泛关注。目前，多款 ATR 抑制剂正处于研发阶段，部分药物已进入临床试验阶段[49–50]。Ceralasertib （AZD6738） 是由阿斯利康开发的一种口服、高选择性 ATR 抑制剂，目前正在进行多项临床试验以评估其在多种类型肿瘤中的安全性和有效性[51–52]。
2.3 CHK 抑制剂
CHK 抑制剂因能够增强放疗和化疗效果而在癌症治疗中受到广泛关注[53]。CHK1 和 CHK2 是 2 种主要的检查点激酶，在细胞周期调控特别是 DNA损伤响应过程中发挥关键作用[54]。CHK1 主要负责在 DNA 损伤时抑制细胞进入有丝分裂，CHK2 则在G1/S 和 G2/M 检查点中发挥作用[55]。CHK 抑制剂通过抑制上述检查点信号通路，阻止癌细胞在 DNA损伤后进行修复，最终导致细胞死亡。在 CHK 类抑制剂中，CHK1 是目前的主要研究靶点。
目前，进入临床研究的 CHK 抑制剂主要包括prexasertib、SRA737、AZD7762、MK-8776 等[56–59]。其中，prexasertib （LY2606368） 的研究进展较为突出。一项针对 BRCA 野生型高级别浆液性卵巢癌患者的Ⅱ期临床试验结果证实，prexasertib 具有抗肿瘤活性和可接受的安全性；对于 BRCA 突变型患者，prexasertib 单药或与 olaparib 联用的研究也已进入Ⅰ期临床研究阶段[60]。此外，近期临床研究结果显示，prexasertib 与伊立替康联用治疗复发/难治性促结缔组织增生性小圆细胞肿瘤患者的客观缓解率可达 32% [61]。SRA737 是一种高选择性口服 CHK1 抑制剂，临床前研究表明，其对 PARP 抑制剂耐药的BRCA 突变及 CCNE1 扩增型卵巢癌模型具有显著抗肿瘤活性，并能延长荷瘤动物的生存期，为该药物在特定分子分型患者中的后续临床开发提供了依据[62]。一项 AZD7762 与吉西他滨联用的 I 期临床试验结果显示，尽管在部分晚期实体瘤患者中观察到抗肿瘤活性，但出现了不可预测的剂量限制性心脏毒性；其与吉西他滨（1 000 mg‧m-2）联用时的最大耐受剂量被确定为 30 mg，最终因心脏毒性问题，AZD7762 的临床开发被迫终止[63]。
2.4 USP1, POLQ, DNA-PKcs 抑制剂
随着对合成致死治疗机制的深入研究，泛素特异性蛋白酶 1（ubiquitin-specific peptidase 1，USP1）、DNA 聚合酶 θ （polymerase theta，POLQ） 和 DNA依赖性蛋白激酶催化亚基 （DNA-dependent protein kinase catalytic subunit，DNA-PKcs） 抑制剂作为新兴潜力靶点逐渐成为领域内的研究热点[64]。
USP1 是一种去泛素化酶，在 DNA 损伤修复过程中发挥重要作用。USP1 通过去除泛素修饰，可调控同源重组修复过程中 DNA 修复蛋白的稳定性。USP1 抑制剂通过干扰 DNA 修复机制，增强肿瘤细胞对化疗和放疗的敏感性。研究表明，多款 USP1抑制剂已在临床前研究中显示出抗肿瘤活性，部分药物已进入Ⅰ期临床试验阶段[65]。
POLQ 是一种 DNA 合成酶，主要参与 DNA 断裂修复。POLQ 抑制剂通过阻断该修复途径，可增强癌细胞对其他 DNA 损伤修复机制的依赖。POLQ在卵巢癌、乳腺癌等多种癌症中呈过表达，因此靶向 POLQ 有望成为特定类型癌症的潜在治疗新策略。近期研究表明，POLQ 抑制剂与其他 DNA 损伤修复抑制剂联用能显著提高疗效，且对 BRCA1/2 缺陷型肿瘤细胞具有特异性杀伤作用[66]。
DNA-PKcs 是非同源末端连接修复通路的关键酶，在 DNA 双链断裂修复过程中发挥重要作用[67]。DNA-PKcs 抑制剂通过抑制该通路，增加肿瘤细胞内 DNA 损伤的积累，促进细胞死亡。目前已有DNA-PKcs 抑制剂 （如 NU7441） 进入临床试验阶段，并展现出良好的治疗潜力。初步临床结果表明，DNA-PKcs 抑制剂能增强放疗效果，且与其他 DNA修复抑制剂联用可能产生协同抗肿瘤作用[68]。
2.5 合成致死类药物的血液学毒性
在合成致死策略下，该疗法尽管能有效诱导肿瘤细胞死亡，也难以避免对正常高增殖细胞产生影响，造血系统尤为显著。正常造血干细胞增殖活跃，并高度依赖 DNA 损伤修复机制。当合成致死疗法靶向关键修复通路时，这些细胞可能因修复受阻而发生 DNA 损伤积累，最终诱导细胞凋亡[69]。因此，血液学毒性成为此类药物研发中的核心安全性问题[70]，其主要临床表现为骨髓抑制，包括贫血、白细胞减少和血小板减少等（见表 1）。
3
QSP 模型引导的合成致死类药物临床转化
3.1 探索合成致死类药物疗效的 QSP 模型
考虑到合成致死类药物作用通路的复杂性及潜在的血液毒性风险，该领域药物研发需引入新的系统方法，在保证合成致死类药物抗肿瘤活性的同时，优化疗效与毒性的平衡，从而提升该类药物的临床可用性与安全性。QSP 建模是一种新兴的药理学研究方法，其整合系统生物学和定量药理学的研究手段，通过构建数学模型定量分析药物与生物系统之间的动态相互作用[87]。QSP 模型能够整合从分子、细胞、组织、器官到整个人体的多尺度生理病理调控事件，从而系统性地描述和预测药物的临床疗效和毒性。近年来，QSP 模型已在全球前沿新药研发中发挥了重要作用[88–91]。
在抗肿瘤药物的临床试验设计中，传统的经验型药理模型通常基于药物已知量-效关系预测临床研究的用药剂量。然而，在合成致死类药物联用治疗等复杂临床场景中，经验型模型往往难以充分解析不同靶点药物之间的动态交互关系，也无法有效揭示联合用药中合成致死效应的协同机制与疗效基础。相比之下，QSP 模型通过整合系统层面的病理和药理机制，能够更精准地刻画合成致死通路中的多靶点协同效应与联合疗效（见表 2）。
Checkley 等[92]构建了一种机制性数学模型，用于指导 ATR 抑制剂 ceralasertib 的临床剂量选择和给药方案设计。该模型整合了细胞周期模块和肿瘤结构模块，能够描述肿瘤细胞在活性增殖的肿瘤外壳和惰性增殖的肿瘤内核之间的转移过程。具体而言，活性增殖外壳中的肿瘤细胞能够进行细胞周期进程（G1-S-G1/M 期），并在此过程中产生 DNA 损伤细胞；内核中的细胞则处于细胞周期停滞状态。当给予 ceralasertib 时，它通过抑制 DNA 损伤的修复，促进细胞死亡，从而耗竭活性增殖的肿瘤外壳。随后，来自惰性内核的肿瘤细胞会取代外壳中的肿瘤细胞，导致肿瘤总体积的缩小。整合后的 QSP 模型成功再现了小鼠异种移植瘤实验模型中不同给药方案下的肿瘤生长变化等数据。该模型进一步预测了ceralasertib 单药治疗的临床疗效以及在不同剂量下与放疗联合用药的疗效，并通过肿瘤体积模拟确定了潜在临床有效剂量，从而为该药物的临床剂量选择提供科学依据。
在合成致死类药物治疗中，肿瘤患者对同一治疗方案的应答可能呈现高度异质性，并呈动态演变特征。部分患者可能存在原发耐药，另有部分患者在初始治疗缓解后可能出现获得性耐药，最终导致疾病进展。为应对此类挑战，联合治疗策略已成为当前研究的热点[98]。目前已有多项临床试验评估了合成致死类药物联用方案 （如 PARP 抑制剂与 ATR抑制剂联用）的治疗潜力[99–100]。
Pugh 等[93]探 究 了 ATR 抑 制 剂 ceralasertib 和PARP 抑制剂 olaparib 在 ATM 缺失型肿瘤细胞中的联合作用。相较于 Checkley 等[92]开发的模型，此模型在结构上更为简化，仅通过细胞周期模块描述肿瘤细胞的增殖情况而未包含详细的肿瘤结构信息。此 外 ， 该 模 型 描 述 了 2 种 药 物 的 作 用 机 制 ：ceralasertib 不仅抑制 S 期损伤细胞的修复，还加速G2/M 期损伤细胞的死亡；olaparib 则促进 G1期细胞损伤并抑制 G2期损伤细胞的修复。研究人员利用体外细胞毒性实验数据对模型参数进行校准，以预测不同剂量下联合用药的体外疗效，并证实联合效果优于单药加和，提示两药具有潜在协同作用。模型分析进一步表明，将 olaparib 剂量提高至 5 μmol‧L-1并固定 ceralasertib 剂量为 0.3 μmol‧L-1，可使细胞活性降低至初始水平的 10%，显著增强抗肿瘤药效。该研究为低剂量短程联合用药方案提供了理论依据，表明数学机制性模型可提前筛选最优剂量组合，降低实验成本，后续还可将模型预测扩展至体内层面以指导临床给药方案设计。
Villette 等[94]也构建了一种临床前 QSP 模型，旨在指导 DDR 联合疗法 （PARP 抑制剂和 ATR 抑制剂） 的转化研究。该模型采用 PARP 抑制剂rucaparib 和 talazoparib 及 ATR 抑制剂 gartisertib 的临床前动物体内数据校准模型参数，成功描述了rucaparib 和 talazoparib 的 单 药 治 疗 效 果 及 与gartisertib 的联用治疗效果。该模型的药效学部分主要由细胞周期模块和 DDR 模块组成。其中，DDR模 块 详 细 刻 画 了 2 种 DNA 损 伤 类 型 （SSB 和DSB），并假设每种损伤均存在 2 条平行的修复途径：2 条由 PARP 介导，另 2 条由 ATR 介导。该模型成功重现了不同实验组 （包括 BRCA 突变、HRD阳性或阴性） 在单药和联合治疗下的小鼠体内肿瘤生长抑制数据，并揭示了在致病机制驱动基础上，无需引入额外的“协同因子”，即可自然产生联合用药的协同效应。此外，该模型还成功预测了 PARP抑制剂与 ATR 抑制剂联用在间歇给药方案下的疗效，证明该联合用药方案在间歇给药时仍具有抗肿瘤能力。该 QSP 模型框架为未来 DDR 靶向治疗的机制研究及临床试验设计 （如临床剂量优化和给药策略设计）提供了高效的高通量模拟工具。
3.2 使用 QSP 模型描述合成致死类药物引起的血液学毒性
合成致死类药物通常伴随一定程度的血液学毒性，主要源于对其 DNA 修复或细胞周期通路的靶向作用，从而影响正常造血系统中依赖上述通路维持基因组稳定性的细胞功能。造血系统细胞的动态变化受复杂的增殖分化网络及细胞因子调控，当关键通路被抑制时，处于增殖期的细胞尤其易受损[101–102]。为定量解析这一过程，QSP 模型可为血液学毒性的机制研究与临床风险预测提供重要依据，通过分析药物对造血系统的时序性影响，支持血液学毒性风险评估与给药策略优化。鉴于合成致死类药物血液学毒性预测模型的框架总体与文献中化疗药物血液学毒性研究所使用的模型框架类似，下文将基于该框架展开论述。
Friberg 模型是血液学毒性研究中较为经典且应用广泛的定量药理模型，其核心包括 3 个组成部分：细胞增殖、细胞迁移 （从骨髓至外周血的传导） 以及负反馈调节[95]。该模型参数主要分为两大类：一类是描述人体造血系统固有特性的系统参数 （包括基线细胞计数、平均成熟时间和反馈强度），另一类是反映药物毒性强度的药物参数 （如药效强度或半效浓度）。在模型构建过程中，研究人员首先基于多西他赛、紫杉醇和依托泊苷的临床数据 （共 1 000余例患者，近 5 000 个观测点） 进行模型开发和参数估计。随后，利用 2'-脱氧-2'-亚甲基胞苷、伊立替康和长春氟宁的独立数据集 （共 200 余例患者，1 700 余个观测点）对模型的预测性能进行验证。总体而言，该模型对不同化疗药物引起的中性粒细胞和白细胞动态变化过程具有良好的描述潜力，在简化复杂生理机制的同时保持较好的预测准确性，已成为评估化疗药物和血液学毒性药物骨髓抑制效应的经典框架[101–103]，由于其机制的可迁移性，该模型也被多次应用于合成致死类药物的血液学毒性预测。
在 Friberg 模型基础上，Ho 等[96]进一步将粒细胞 集 落 刺 激 因 子 （granulocyte colony-stimulating factor，G-CSF） 信号通路及中性粒细胞边缘池纳入定量模型预测体系。该研究构建了从中性粒细胞凋亡驱动白介素 23 产生，经 T 细胞活化、白介素 17释放，最终促使基质细胞分泌 G-CSF 的信号通路，从而实现对内源性 G-CSF 调控机制的动态模拟。同时，该模型引入与细胞循环池处于动态平衡的边缘池，用以描述炎症状态下中性粒细胞自血管壁储备快速动员入血的生理过程，弥补了原模型在急性炎症响应描述方面的不足。在模型构建方法上，研究人员首先基于稳态水平确定基础生理参数，结合 G-CSF 外源给药数据校准其药动学‑药效学关系，再分别利用脂多糖刺激实验数据与多西他赛化疗临床数据，对炎症快速响应模块与化疗骨髓抑制模块进行针对性参数估计。该模型在统一框架下实现了对炎症 （快速） 与化疗 （慢速） 2 种不同时间尺度所引起中性粒细胞动态响应的机制性描述，同时也为其他血液学细胞毒性预测提供一定参考。
Friberg 模型与 Ho 模型分别代表了血液学毒性建模研究的不同发展阶段。Friberg 模型凭借其参数精简、可迁移性强的特点，已在临床前至临床转化阶段的药物毒性比较与剂量优化中得到广泛应用。然而，该模型对生理机制的简化处理也使其存在一定局限。在此背景下，Ho 模型通过引入 G-CSF 信号通路及中性粒细胞边缘池动态，显著提升了模型的生理相关性及预测广度。然而，Ho 模型结构复杂，参数校准难度较高，计算成本也相应增加，这在一定程度上限制了其在数据稀疏的早期研究中的应用。未来，该领域模型的优化方向将主要集中于2 个方面：一是在维持模型机制完整性的基础上，通过模块化设计 （如区分基础造血模块与炎症响应模块） 提升模型的灵活性与可解释性；二是进一步整合多组学数据（如不同细胞亚群的动态信息），以提高模型参数精度与个体化预测能力。
此外，Wilson 等[97]基于体外多谱系造血实验构建了 QSP 模型，以解析药物对不同造血谱系的特异性作用机制。研究人员首先利用人源 CD34+造血干细胞在无药条件下的增殖-分化动力学数据，建立了包含 13 个细胞群体的造血系统基准模型。随后，通过测试 51 种化合物在多谱系毒性实验中的浓度-效应数据，采用反卷积分析方法将观测到的整体细胞毒性效应分解为针对各细胞谱系的特异性机制参数。基于模型，研究人员将药物效应区分为抗增殖与细胞杀伤 2 种机制，实现了对药物作用模式的精确量化。模型通过主成分分析成功区分不同作用机制的化合物类别，并在已知机制的参考药物上验证了其预测准确性。该 QSP 模型研究为早期候选化合物的骨髓抑制风险评估提供了新的思路，并增强了模型引导体外-体内毒性外推的可解释性。
4
结语与展望
合成致死策略在癌症治疗中具有重要意义，但其机制网络极为复杂，涉及多种细胞通路和补偿机制。细胞在面临基因突变或 DNA 损伤时，会启动一系列修复机制以维持基因组稳定性。然而，当主要修复通路受阻时，细胞可激活替代通路，如跨损伤合成 （translesion synthesis，TLS）、Alt-EJ 和单链退火等修复通路[103–105]。此类替代通路虽效率较低，但可部分补偿主要通路的功能，从而维持细胞生存。此外，细胞内信号传导网络也会在基因突变后重新调整，以适应新的生理状态。例如，已有研究发现在 DNA 损伤存在的情况下，蛋白激酶 B （protein kinase B，PKB，又称 AKT） 和细胞外调节蛋白激酶 （extracellular regulated protein kinase，ERK） 等通路的激活仍可促进细胞存活[106]。因此，合成致死领域的 QSP 模型需根据研究目的，持续整合新兴的旁路通路激活机制和治疗靶点，以增强模型对复杂系统中新药联用策略的综合预测能力。
笔者团队已围绕合成致死类药物的多个主要靶点 （包括 PARP、USP1、POLQ、WEE1、CHK1、ATR、DNA-PKcs） 构建了一个整合药物 PK、细胞周期多点调控、DNA 损伤应答信号通路及血液学毒性的机制性 QSP 模型平台，旨在指导该领域候选新药的临床转化研发。该模型平台可同时描述多靶点治疗机制，系统刻画单药及药物联用方案下细胞周期与 DNA 损伤通路之间的协同或拮抗作用，进而从机制层面揭示不同作用靶点与给药策略对抗肿瘤治疗疗效与血液学安全性的影响。通过基于 QSP 模型的虚拟患者构建和虚拟临床试验分析，研究人员可运用模型探索候选新药的临床剂量-反应关系，分析不同谱系血细胞对药物诱导毒性的差异，推荐临床初始剂量、剂量递增方案（包括最大耐受剂量/最优生物学剂量的确定） 以及Ⅱ/Ⅲ期扩展剂量，并为候选药物及其组合的安全性评估、优先级排序及临床剂量优化 （包括间歇给药方案设计） 提供量化决策依据和监管审评支撑。值得注意的是，在运用QSP 模型进行临床模拟时需全面考虑小分子合成致死药物及其组合因个体代谢差异导致的临床疗效和毒性差异，并需结合研究目标考虑用药过程中的潜在耐药机制，从而实现对合成致死类药物疗效持久性的更准确预测。总体而言，合成致死类药物的QSP 模型平台及相关虚拟临床试验分析可在提升新药临床试验效率的同时，降低受试者安全风险，并为合成致死类药物的临床开发与审评决策提供可解释、可量化的科学支撑。
参考文献：
[1]Dobzhansky T. Genetics of natural populations. xiii.recombination and variability in populations of Drosophila pseudoobscura[J]. Genetics, 1946, 31(3): 269-290.
[2]Nijman S M B. Synthetic lethality: general principles, utility and detection using genetic screens in human cells[J]. Febs Letters, 2011, 585(1): 1-6.
[3]Hartwell L H, Szankasi P, Roberts C J, et al. Integrating genetic approaches into the discovery of anticancer drugs[J].Science, 1997, 278(5340): 1064-1068.
[4]Bryant H E, Schultz N, Thomas H D, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase[J]. Nature, 2005, 434(7035): 913-917.
[5]Farmer H, McCabe N, Lord C J, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy[J].Nature, 2005, 434(7035): 917-921.
[6]Lee J M, Ledermann J A, Kohn E C. PARP inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies[J].Ann Oncol, 2014, 25(1): 32-40.
[7]Levy-Lahad E, Friedman E. Cancer risks among BRCA1 and BRCA2 mutation carriers[J]. Br J Cancer, 2007, 96(1): 11-15.
[8]Chabanon R M, Muirhead G, Krastev D B, et al. PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer[J]. J Clin Invest, 2019, 129(3): 1211-1228.
[9]Cavanagh H, Rogers K M A. The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers[J]. Hered Cancer Clin Pract, 2015, 13(1): 16.
[10] Kim G, Ison G, McKee A E, et al. FDA approval summary:olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy[J]. Clin Cancer Res, 2015, 21(19):4257-4261.
[11] Freeman A K, Monteiro A N. Phosphatases in the cellular response to DNA damage[J]. Cell Commun Signal, 2010, 8: 27.
[12] Schmitt E, Paquet C, Beauchemin M, et al. DNA-damage response network at the crossroads of cell-cycle checkpoints,cellular senescence and apoptosis[J]. J Zhejiang Univ Sci B,2007, 8(6): 377-397.
[13] Ye Z, Shi Y, Lees-Miller S P, et al. Function and molecular mechanism of the DNA damage response in immunity and cancer immunotherapy[J]. Front Immunol, 2021, 12: 797880.
[14] Chen X J. Mechanism of homologous recombination and implications for aging-related deletions in mitochondrial DNA[J]. Microbiol Mol Biol Rev, 2013, 77(3): 476-496.
[15] Kim J S, Krasieva T B, Kurumizaka H, et al. Independent and sequential recruitment of NHEJ and HR factors to DNA damage sites in mammalian cells[J]. J Cell Biol, 2005, 170(3):341-347.
[16] Huang R X, Zhou P K. DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer[J]. Signal Transduct Target Ther, 2020, 5(1): 60.
[17] Gohil D, Sarker A H, Roy R. Base excision repair: mechanisms and impact in biology, disease, and medicine[J]. Int J Mol Sci,2023, 24(18): 14186.
[18] Caldecott K W. Single-strand break repair and genetic disease[J]. Nat Rev Genet, 2008, 9(8): 619-631.
[19] Patil M, Pabla N, Dong Z. Checkpoint kinase 1 in DNA damage response and cell cycle regulation[J]. Cell Mol Life Sci, 2013, 70(21): 4009-4021.
[20] Smith J, Tho L M, Xu N, et al. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer[J]. Adv Cancer Res, 2010, 108: 73-112.
[21] Bukhari A B, Chan G K, Gamper A M. Targeting the DNA damage response for cancer therapy by inhibiting the kinase Wee1[J]. Front Oncol, 2022, 12: 828684.
[22] Li Q, Qian W, Zhang Y, et al. A new wave of innovations within the DNA damage response[J]. Signal Transduct Target Ther, 2023, 8: 338.
[23] Fountzilas E, Papadopoulou K, Chatzikonstantinou T, et al.Concordance between three homologous recombination deficiency (HRD) assays in patients with high-grade epithelial ovarian cancer[J]. Cancers, 2023, 15(23): 5525.
[24] Cristescu R, Liu X Q, Arreaza G, et al. Concordance between single-nucleotide polymorphism-based genomic instability assays and a next-generation sequencing-based homologous recombination deficiency test[J]. BMC Cancer, 2022, 22(1):1310.
[25] Jia Z, Liu Y, Qu S, et al. Evaluative methodology for HRD testing: development of standard tools for consistency assessment[J]. Genomics Proteomics Bioinformatics, 2025, 23(1): qzaf017.
[26] Christie E L, Fereday S, Doig K, et al. Reversion of BRCA1/2 germline mutations detected in circulating tumor DNA from patients with high-grade serous ovarian cancer[J]. J Clin Oncol, 2017, 35(12): 1274-1280.
[27] Noordermeer S M, van Attikum H. PARP inhibitor resistance: a tug-of-war in BRCA-mutated cells[J]. Trends Cell Biol, 2019, 29(10): 820-834.
[28] Giudice E, Gentile M, Salutari V, et al. PARP inhibitors resistance: mechanisms and perspectives[J]. Cancers, 2022, 14(6): 1420.
[29] Friedlander M, Lee Y C, Tew W P. Managing adverse effects associated with poly (ADP-ribose) polymerase inhibitors in ovarian cancer: a synthesis of clinical trial and real-world data[J]. Am Soc Clin Oncol Educ Book, 2023(43): e390876.
[30] LaFargue C J, Dal Molin G Z, Sood A K, et al. Exploring and comparing adverse events between PARP inhibitors[J]. Lancet Oncol, 2019, 20(1): e15-e28.
[31] Zheng J, Li Z, Min W. Current status and future promise of next-generation poly(ADP-Ribose) polymerase 1-selective inhibitor AZD5305[J]. Front Pharmacol, 2023, 13: 979873.
[32] Zhou T, Zhang J. Therapeutic advances and application of PARP inhibitors in breast cancer[J]. Transl Oncol, 2025, 57:102410.
[33] Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer[J].N Engl J Med, 2018, 379(26): 2495-2505.
[34] Pilié P G, Gay C M, Byers L A, et al. PARP inhibitors: extending benefit beyond BRCA-mutant cancers[J]. Clin Cancer Res, 2019, 25(13): 3759-3771.
[35] Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial[J]. Lancet Oncol, 2014, 15(8): 852-861.
[36] Markham A. Pamiparib: first approval[J]. Drugs, 2021, 81(11):1343-1348.
[37] Lee A. Fuzuloparib: first approval[J]. Drugs, 2021, 81(10):1221-1226.
[38] Murai J, Huang S N, Das B B, et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors[J]. Cancer Res, 2012, 72(21): 5588-5599.
[39] Kim D S, Camacho C V, Kraus W L. Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance[J]. Exp Mol Med, 2021, 53(1): 42-51.
[40] Onji H, Murai J. Reconsidering the mechanisms of action of PARP inhibitors based on clinical outcomes[J]. Cancer Sci, 2022, 113(9): 2943-2951.
[41] Ronson G E, Piberger A L, Higgs M R, et al. PARP1 and PARP2 stabilise replication Forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation[J].Nat Commun, 2018, 9(1): 746.
[42] Farrés J, Martín-Caballero J, Martínez C, et al. PARP-2 is required to maintain hematopoiesis following sublethal γ-irradiation in mice[J]. Blood, 2013, 122(1): 44-54.
[43] Illuzzi G, Staniszewska A D, Gill S J, et al. Preclinical characterization of AZD5305, a next-generation, highly selective PARP1 inhibitor and trapper[J]. Clin Cancer Res,2022, 28(21): 4724-4736.
[44] Yano K, Shiotani B. Emerging strategies for cancer therapy by ATR inhibitors[J]. Cancer Sci, 2023, 114(7): 2709-2721.
[45] Karnitz L M, Zou L. Molecular pathways: targeting ATR in cancer therapy[J]. Clin Cancer Res, 2015, 21(21): 4780-4785.
[46] Ngoi N Y L, Pilié P G, McGrail D J, et al. Targeting ATR in patients with cancer[J]. Nat Rev Clin Oncol, 2024, 21(4):278-293.
[47] Toledo L I, Murga M, Gutierrez-Martinez P, et al. ATR signaling can drive cells into senescence in the absence of DNA breaks[J]. Genes Dev, 2008, 22(3): 297-302.
[48] Hanahan D, Weinberg R A. Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5): 646-674.
[49] Barnieh F M, Loadman P M, Falconer R A. Progress towards a clinically-successful ATR inhibitor for cancer therapy[J]. Curr Res Pharmacol Drug Discov, 2021, 2: 100017.
[50] Priya B, Ravi S, Kirubakaran S. Targeting ATM and ATR for cancer therapeutics: inhibitors in clinic[J]. Drug Discov Today,2023, 28(8): 103662.
[51] Kwon M, Kim S T, Smith S, et al. Phase II study of ceralasertib (AZD6738), in combination with durvalumab in patients with metastatic melanoma who have failed prior anti-PD-1 therapy[J]. J Clin Oncol, 2021, 39(15_Suppl): 9514.
[52] Costa P A, Hafez N, Pilat M J P, et al. A phase 2 study of the olaparib and AZD6738, an ATM/ATR inhibitor, in isocitrate dehydrogenase (IDH) mutant solid tumors[J]. J Clin Oncol,2025, 43(16_Suppl): 3089.
[53] Qiu Z, Oleinick N L, Zhang J. ATR/CHK1 inhibitors and cancer therapy[J]. Radiother Oncol, 2018, 126(3): 450-464.
[54] Hammond E M, Freiberg R A, Giaccia A J. The roles of CHK 1 and CHK 2 in hypoxia and reoxygenation[J]. Cancer Lett,2006, 238(2): 161-167.
[55] Minchom A, Aversa C, Lopez J. Dancing with the DNA damage response: next-generation anti-cancer therapeutic strategies[J].Ther Adv Med Oncol, 2018, 10: 1758835918786658.
[56] Angius G, Tomao S, Stati V, et al. Prexasertib, a checkpoint kinase inhibitor: from preclinical data to clinical development[J]. Cancer Chemothery Pharmacol, 2020, 85(1): 9-20.
[57] Engelke C G, Parsels L A, Qian Y, et al. Sensitization of pancreatic cancer to chemoradiation by the CHK1 inhibitor MK8776[J]. Clin Cancer Res, 2013, 19(16): 4412-4421.
[58] Plummer E R, Kristeleit R S, Cojocaru E, et al. A first-in-human phase I/II trial of SRA737 (a CHK1 inhibitor) in subjects with advanced cancer[J]. J Clini Oncol, 2019, 37(15_Suppl): 3094-3094.
[59] Zhu J, Zou H, Yu W, et al. Checkpoint kinase inhibitor AZD7762 enhance cisplatin-induced apoptosis in osteosarcoma cells[J]. Cancer Cell Int, 2019, 19: 195.
[60] Evangelisti G, Barra F, Moioli M, et al. Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer[J]. Expert Opin Investig Drugs, 2020, 29(8): 779-792.
[61] Slotkin E K, Mauguen A, Dela Cruz F S, et al. ACR-368, a CHK1/2 kinase inhibitor, in patients with relapsed or refractory desmoplastic small round cell tumor: phase I/II trial results[J]. JCO Oncol Adv, 2025, 2(1): e2400095.
[62] Xu H, Gitto S B, Ho G Y, et al. CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and CCNE1 amplified ovarian cancer[J]. iScience, 2024, 27(7): 109978.
[63] Sausville E, Lorusso P, Carducci M, et al. Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors[J]. Cancer Chemother Pharmacol, 2014, 73(3):539-549.
[64] Cheng B, Ding Z, Hong Y, et al. Research progress in DNA damage response (DDR) -targeting modulators: from hits to clinical candidates[J]. Eur J Med Chem, 2025, 287: 117347.
[65] Torrado C, Ashton N W, D,Andrea A D, et al. USP1 inhibition:a journey from target discovery to clinical translation[J].Pharmacol Ther, 2025, 271: 108865.
[66] da Costa A A, Somuncu O, Ravindranathan R, et al. Single-stranded DNA gap accumulation is a functional biomarker for USP1 inhibitor sensitivity[J]. Cancer Res, 2024, 84(20): 3435-3446.
[67] Dylgjeri E, Knudsen K E. DNA-PKcs: a targetable protumorigenic protein kinase[J]. Cancer Res, 2022, 82(4):523-533.
[68] Ohuchi K, Saga R, Hasegawa K, et al. DNA-PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells[J]. Biomed Rep, 2023, 18(4): 28.
[69] Dhillon K K, Bajrami I, Taniguchi T, et al. Synthetic lethality:the road to novel therapies for breast cancer[J]. Endocr Relat Cancer, 2016, 23(10): T39-T55.
[70] Mahmood R D, Morgan R D, Edmondson R J, et al. First-line management of advanced high-grade serous ovarian cancer[J].Curr Oncol Rep, 2020, 22(6): 64.
[71] Poveda A, Floquet A, Ledermann J A, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2021, 22(5):620-631.
[72] Monk B J, Barretina-Ginesta M P, Pothuri B, et al. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial[J]. Ann Oncol, 2024, 35(11): 981-992.
[73] Oza A M, Lisyanskaya A, Fedenko A, et al. Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial[J]. Lancet Oncol, 2025, 26(2): 249-264.
[74] Fizazi K, Azad A A, Matsubara N, et al. First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial[J]. Nat Med, 2024, 30(1): 257-264.
[75] Li N, Zhang Y, Wang J, et al. Fuzuloparib maintenance therapy in patients with platinum-sensitive, recurrent ovarian carcinoma (FZOCUS-2): a multicenter, randomized, double-blind, placebo-controlled, phase III trial[J]. J Clin Oncol, 2022,40(22): 2436-2446.
[76] Kwon M, Kim G, Kim R, et al. Phase II study of ceralasertib(AZD6738) in combination with durvalumab in patients with advanced gastric cancer[J]. J Immunother Cancer, 2022, 10(7):e005041.
[77] Konstantinopoulos P A, Cheng S C, Wahner Hendrickson A E,et al. Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial[J]. Lancet Oncol, 2020, 21(7): 957-968.
[78] Yap T A, Tan D S P, Stathis A, et al. Phase ib basket expansion trial and alternative-schedule dose-escalation study of ATR inhibitor elimusertib in advanced solid tumors with DNA damage response defects[J]. Cancer Discov, 2025, 15(10):2019-2035.
[79] Yap T A, Fontana E, Lee E K, et al. Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results[J]. Nat Med, 2023, 29(6): 1400-1411.
[80] Konstantinopoulos P A, Lee J M, Gao B, et al. A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer[J]. Gynecol Oncol, 2022, 167(2):213-225.
[81] Kristeleit R, Plummer R, Jones R, et al. A Phase 1/2 trial of SRA737 (a CHK1 inhibitor) administered orally in patients with advanced cancer[J]. Br J Cancer, 2023, 129(1): 38-45.
[82] Huffman B M, Feng H, Parmar K, et al. A phase I expansion cohort study evaluating the safety and efficacy of the CHK1 inhibitor LY2880070 with low-dose gemcitabine in patients with metastatic pancreatic adenocarcinoma[J]. Clin Cancer Res, 2023, 29(24): 5047-5056.
[83] Daud A I, Ashworth M T, Strosberg J, et al. Phase I dose-escalation trial of checkpoint kinase 1 inhibitor MK-8776 as monotherapy and in combination with gemcitabine in patients with advanced solid tumors[J]. J Clin Oncol, 2015, 33(9):1060-1066.
[84] Yap T A, Lakhani N J, Patnaik A, et al. First-in-human phase I trial of the oral first-in-class ubiquitin specific peptidase 1 (USP1) inhibitor KSQ-4279 (KSQi), given as single agent(SA) and in combination with olaparib (OLA) or carboplatin(CARBO) in patients (pts) with advanced solid tumors, enriched for deleterious homologous recombination repair (HRR) mutations[J]. J Clin Oncol, 2024, 42(16_Suppl): 3005.
[85] Romesser P B, Capdevila J, Garcia-Carbonero R, et al. A phase Ib study of the DNA-PK inhibitor peposertib combined with neoadjuvant chemoradiation in patients with locally advanced rectal cancer[J]. Clin Cancer Res, 2024, 30(4): 695-702.
[86] Yap T A, LoRusso P, Miller R E, et al. The DNA-PK inhibitor AZD7648 alone or combined with pegylated liposomal doxorubicin in patients with advanced cancer: results of a first-in-human phase I/IIa study[J]. Br J Cancer, 2025, 133(2):168-177.
[87] Azer K, Kaddi C D, Barrett J S, et al. History and future perspectives on the discipline of quantitative systems pharmacology modeling and its applications[J]. Front Physiol,2021, 12: 637999.
[88] Helmlinger G, Sokolov V, Peskov K, et al. Quantitative systems pharmacology: an exemplar model-building workflow with applications in cardiovascular, metabolic, and oncology drug development[J]. CPT Pharmacometrics Syst Pharmacol,2019, 8(6): 380-395.
[89] Wang H, Ma H, Sové R J, et al. Quantitative systems pharmacology model predictions for efficacy of atezolizumab and nab-paclitaxel in triple-negative breast cancer[J]. J Immunother Cancer, 2021, 9(2): e002100.
[90] Hosseini I, Mac Gabhann F. Mechanistic models predict efficacy of CCR5-deficient stem cell transplants in HIV patient populations[J]. CPT Pharmacometrics Syst Pharmacol, 2016, 5(2): 82-90.
[91] Coletti R, Leonardelli L, Parolo S, et al. A QSP model of prostate cancer immunotherapy to identify effective combination therapies[J]. Sci Rep, 2020, 10(1): 9063.
[92] Checkley S, MacCallum L, Yates J, et al. Bridging the gap between in vitro and in vivo: dose and schedule predictions for the ATR inhibitor AZD6738[J]. Sci Rep, 2015, 5: 13545.
[93] Pugh K, Davies M, Powathil G. A mathematical model to investigate the effects of ceralasertib and olaparib in targeting the cellular DNA damage response pathway[J]. J Pharmacol Exp Ther, 2023, 387(1): 55-65.
[94] Villette C C, Dupuy N, Brightman F A, et al. Semi-mechanistic efficacy model for PARP+ATR inhibitors: application to rucaparib and talazoparib in combination with gartisertib in breast cancer PDXs[J]. Br J Cancer, 2025, 132(5): 481-491.
[95] Friberg L E, Henningsson A, Maas H, et al. Model of chemotherapy-induced myelosuppression with parameter consistency across drugs[J]. J Clin Oncol, 2002, 20(24): 4713-4721.
[96] Ho T, Clermont G, Parker R S. A model of neutrophil dynamics in response to inflammatory and cancer chemotherapy challenges[J]. Comput Chem Eng, 2013, 51: 187-196.
[97] Wilson J L, Lu D, Corr N, et al. An in vitro quantitative systems pharmacology approach for deconvolving mechanisms of drug-induced, multilineage cytopenias[J]. PLoS Comput Biol, 2020, 16(7): e1007620.
[98] Dias M P, Moser S C, Ganesan S, et al. Understanding and overcoming resistance to PARP inhibitors in cancer therapy[J]. Nat Rev Clin Oncol, 2021, 18(12): 773-791.
[99] Shah P D, Wethington S L, Pagan C, et al. Combination ATR and PARP Inhibitor (CAPRI): a phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-resistant epithelial ovarian cancer[J]. Gynecol Oncol, 2021, 163(2):246-253.
[100] Wethington S L, Shah P D, Martin L, et al. Combination ATR (ceralasertib) and PARP (olaparib)inhibitor (CAPRI) trial in acquired PARP inhibitor-resistant homologous recombination-deficient ovarian Cancer[J]. Clin Cancer Res, 2023, 29(15): 2800-2807.
[101] Craig M. Towards quantitative systems pharmacology models of chemotherapy-induced neutropenia[J]. CPT Pharmacometrics Syst Pharmacol, 2017, 6(5): 293-304.
[102] Fornari C, Oplustil O’Connor L, Pin C, et al. Quantifying drug-induced bone marrow toxicity using a novel haematopoiesis systems pharmacology model[J]. CPT Pharmacometrics Syst Pharmacol, 2019, 8(11): 858-868.
[103] Iliakis G, Murmann T, Soni A. Alternative end-joining repair pathways are the ultimate backup for abrogated classical non-homologous end-joining and homologous recombination repair: implications for the formation of chromosome translocations[J]. Mutat Res Genet Toxicol Environ Mutagen,2015, 793: 166-175.
[104] Bhargava R, Onyango D O, Stark J M. Regulation of single-strand annealing and its role in genome maintenance[J]. Trends Genet, 2016, 32(9): 566-575.
[105] Haynes B, Saadat N, Myung B, et al. Crosstalk between translesion synthesis, Fanconi anemia network, and homologous recombination repair pathways in interstrand DNA crosslink repair and development of chemoresistance[J].Mutat Res Mutat Res, 2015, 763: 258-266.
[106] Guenther M K, Graab U, Fulda S. Synthetic lethal interaction between PI3K/Akt/mTOR and Ras/MEK/ERK pathway inhibition in rhabdomyosarcoma[J]. Cancer Lett, 2013, 337(2):200-209.
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肖霞, 洪峻, 边康麒, 等. 合成致死类药物的定量系统药理模型研究与应用进展[J]. 药学进展, 2026, 50(6): 485- 495.
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2026-08-31
- Second of five planned cohorts ongoing in Phase 1/2a trial of GLIX1 in GBM; third patient cohort expected to commence dosing in September -
- Announced new data showing GLIX1 achieved potent antitumor activity in TMZ-resistant patient-derived xenograft (PDX) GBM in vivo model -
- Announced additional data demonstrating strong synergistic effect between GLIX1 and PARP inhibitor in patient-derived HR-proficient ovarian cancer xenograft model -
- Management to host conference call today, August 31, at 8:30 am EDT -
TEL AVIV, Israel, Aug. 31, 2026 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, today reported its unaudited financial results for the quarter ended June 30, 2026, and provided a corporate update.
"During the second quarter and subsequent period, we advanced GLIX1 across multiple fronts," stated Philip Serlin, Chief Executive Officer of BioLineRx. "Our Phase 1/2a study in glioblastoma is advancing as planned, with the second cohort in the Phase 1 part now being dosed, and the third cohort expected to commence dosing in September. To date, a little more than four months into the study, we have been very pleased with the drug's safety and tolerability.
"Also, during the quarter, we were excited to demonstrate the potential of GLIX1 to address unmet needs for GBM as well as ovarian cancer in a number of pre-clinical models. In this regard, we announced new data in a temozolomide-resistant patient-derived xenograft (PDX) GBM in-vivo model, in which GLIX1 demonstrated a robust anti-tumor effect while TMZ showed no effect. These results further support GLIX1's potential to treat a broad range of patients with GBM. We also generated data showing strong synergy between GLIX1 and PARP inhibitors in an HR-proficient patient-derived ovarian cancer in-vivo model, and based upon these excellent findings, we are planning to add an ovarian cancer arm to the Phase 2a expansion phase of the trial. Together, these developments keep GLIX1 on track in glioblastoma while extending its reach into additional tumor types where new treatment options are desperately needed."
Financial Updates
With $13.1 million on its balance sheet as of June 30, 2026, BioLineRx is maintaining its cash runway guidance into the first half of 2027.
On August 27, 2026, the Company entered into a definitive agreement for an offering with gross proceeds of $3.75 million, expected to close on or about August 31, 2026.
Development Updates
GLIX1 in GBM
In July, dosing commenced in the second of five planned cohorts in the Phase 1 dose escalation part of the Phase 1/2a study.
Three leading cancer centers are enrolling patients in the Phase 1 part of the study: NYU Langone Health, led by Dr. Alexandra Miller; Northwestern University, led by Dr. Roger Stupp and Dr. Ditte Primdahl; and Moffit Cancer Center, led by Dr. Patrick Grogan.
The Phase 1 part of the trial is expected to recruit up to 30 patients with recurrent and progressive GBM and other high-grade gliomas. The objective is to establish a maximum tolerated dose (MTD) and/or a recommended dose based on safety, PK/PD and preliminary efficacy.
The Phase 2a expansion part of the trial is planned to include various population cohorts, including GBM (newly diagnosed and/or recurrent), as well as additional cancers with/without standard of care (e.g., PARP inhibitors), including an ovarian cancer arm. These cohorts are expected to identify preliminary efficacy, PD assessments and dose optimization data, serving as the basis for rapid and effective advanced clinical development.
New data demonstrated potent anti-tumor effect of GLIX1 in GBM across multiple in-vivo studies, including a temozolomide (TMZ)-resistant patient-derived xenograft model. In the three orthotopic CDX studies, significant tumor growth inhibition and survival benefit were observed following treatment with GLIX1 across all doses tested, with greater benefit at higher dose levels. Most notably, in the subcutaneous PDX model, GLIX1 demonstrated a robust anti-tumor effect while TMZ showed no effect.
Clinical and pre-clinical data have been accepted for publication at the European Association of Neuro-Oncology (EANO) 2026 Conference and at the Society for Neuro-Oncology (SNO) 2026 Annual Meeting.
GLIX1 in combination with PARPi
New data demonstrated strong synergy between GLIX1 and PARP inhibitors, reinforcing synthetic lethality between GLIX1 and PARP inhibitors.
Synergy was demonstrated in a patient-derived xenograft (PDX) in-vivo model of HR-proficient ovarian cancer, where PARP inhibitors have historically had limited efficacy. Results show substantially better efficacy in the combination arm versus the control arm and versus the monotherapy arms, despite using lower doses in the combination arm. Notably, the low-dose GLIX1/olaparib combination tumor reduction was similar to cisplatin, the current chemotherapy benchmark.
An abstract featuring new GLIX1 data, demonstrating synergy with PARP inhibitors in HR-proficient ovarian cancer, was accepted for publication at the 2026 European Society for Medical Oncology Annual Congress (ESMO 2026) in October.
BioLineRx has initiated discussions with leading PARP inhibitor companies to explore potential development collaborations.
Motixafortide
Pancreatic Ductal Adenocarcinoma (mPDAC)
Enrollment is continuing in the CheMo4METPANC Phase 2b clinical trial, which is being led by Columbia University, and supported by both Regeneron and BioLineRx. The trial is evaluating motixafortide in combination with the PD-1 inhibitor cemiplimab and standard chemotherapy (gemcitabine and nab-paclitaxel).
A prespecified interim/futility analysis is planned when 40% of progression-free survival (PFS) events are observed, which the Company continues to anticipate will occur in 2026.
APHEXDA Performance Update
For the second quarter of 2026, APHEXDA sales were $1.6 million, which provided royalty revenue to the Company of $0.3 million.
Financial Results for the Quarter ended June 30, 2026
Revenues for the three months ended June 30, 2026 were $0.3 million, similar to the three months ended June 30, 2025.
Research and development expenses for the three months ended June 30, 2026 were $2.9 million, an increase of $0.6 million, or 26.5%, compared to $2.3 million for the comparable 2025 period. The increase resulted primarily from expenses related to the new GLIX1 project, offset by lower expenses related to motixafortide.
General and administrative expenses for the three months ended June 30, 2026 were $0.9 million, an increase of $0.7 million, or 313.9%, compared to $0.2 million for the comparable 2025 period. The increase resulted from the reversal of a $0.8 million provision for doubtful accounts in the 2025 period following receipt of an overdue milestone payment from Gloria.
Non-operating expenses amounted to $0.7 million for the three months ended June 30, 2026, compared to non-operating expenses of $1.9 million for the three months ended June 30, 2025. Non-operating expenses for both periods primarily relates to fair-value adjustments of warrant liabilities on the Company's balance sheet.
Net financial expenses for the three months ended June 30, 2026 were $0.1 million compared to net financial income of $0.2 million for the three months ended June 30, 2025. Net financial expenses in 2026 primarily relate to interest paid on loans, partially offset by investment income earned on bank deposits. Net financial income in 2025 primarily relates to investment income earned on bank deposits and gains on foreign currency cash balances due to the strengthening of the NIS during the period, partially offset by interest paid on loans.
Net loss for the three months ended June 30, 2026 was $4.3 million, compared to $3.9 million for the three months ended June 30, 2025.
As of June 30, 2026, the Company had cash, cash equivalents, and short-term bank deposits of $13.1 million.
Conference Call and Webcast Information
To access the conference call, please dial +1-888-407-2553 from the U.S. or +972-3-918-0685 internationally. A live webcast and a replay of the call can be accessed through the event page on the Company's website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast. The call replay will be available approximately two hours after completion of the live conference call. A dial-in replay of the call will be available until September 1, 2026; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally.
About BioLineRx
BioLineRx Ltd. (NASDAQ/TASE: BLRX) is a biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases. The Company's lead development asset is GLIX1, a first-in-class, oral, small molecule targeting DNA damage response in glioblastoma and other solid tumors, for which a Phase 1/2a clinical trial was initiated in the first quarter of 2026. GLIX1 is being developed under a collaboration with Hemispherian AS.
The Company's first approved product, APHEXDA® (motixafortide), is indicated in the U.S. for stem cell mobilization for autologous transplantation in multiple myeloma, and is being commercialized by Ayrmid Ltd. (globally, except Asia) and by Gloria Biosciences (in Asia). BioLineRx has retained the rights to develop motixafortide in metastatic pancreatic cancer (PDAC) and has a Phase 2b PDAC trial currently ongoing under a collaboration with Columbia University.
Learn more about who we are, what we do, and how we do it at , or on LinkedIn.
Forward Looking Statement
Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "anticipates," "believes," "could," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," and "would," and describe opinions about future events. These include statements regarding management's expectations, beliefs and intentions regarding, among other things, the expectations with regard to the Phase 1/2a GLIX1 clinical trial, expected timing of a clinical dosing, and BioLineRx's business strategy. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the clinical development, commercialization and market acceptance of GLIX1 and motixafortide including the degree and pace of market uptake of APHEXDA for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients; the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials and other therapeutic candidate development efforts; BioLineRx's ability to advance GLIX1 and motixafortide into clinical trials or to successfully complete its preclinical studies or clinical trials; whether the clinical trial results for GLIX1 and motixafortide will be predictive of real-world results; BioLineRx's receipt of regulatory approvals for GLIX1 and motixafortide and the timing of other regulatory filings and approvals; whether access to GLIX1 and motixafortide is achieved in a commercially viable manner and whether GLIX1 and motixafortide receives adequate reimbursement from third.-party payors; BioLineRx's ability to establish, manage, and maintain corporate collaborations, as well as the ability of BioLineRx's collaborators to execute on their development and commercialization plans; BioLineRx's ability to integrate new therapeutic candidates and new personnel, as well as new collaborations; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection that BioLineRx's is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its need for and ability to access sufficient additional financing; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; BioLineRx's ability to maintain the listing of its ADSs on Nasdaq; statements as to the impact of the political and security situation in Israel on BioLineRx's business which may exacerbate the magnitude of the factors discussed above. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 23, 2026. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.
Contacts:
United States
Chuck Padala
LifeSci Advisors, LLC
[email protected]
Israel
Moran Meir
LifeSci Advisors, LLC
[email protected]
SOURCE BioLineRx Ltd.
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临床1期财报上市批准临床2期临床结果
2026-08-31
Hepatology[Jour] AND 84[volume] AND 1[issue]
肝脏病学 84卷1期
https://journals.lww.com/hep/pages/currenttoc.aspx
Hepatology Highlights（肝病学亮点）
1
Bile acids as the silent harbinger: Early signals of portal hypertension after “successful”Kasai
胆汁酸——沉默的预兆：Kasai术"成功"后的门脉高压早期信号
Sidhu, Guneet
Hepatology. 84(1):1-2, July 2026.
2
What’s in a name? Reframing pediatric fatty liver disease in the Era of MASLD
名称之争：代谢相关脂肪性肝病（MASLD）时代儿童脂肪肝疾病的重新定义
Khalid, Mian B.; Ilyas, Sumera I.
Hepatology. 84(1):3-4, July 2026.
3
One size does not fit all: Global variability in noninvasive testing for MASLD
一刀切不可取：MASLD无创检测的全球差异性
Erickson, Hanna
Hepatology. 84(1):5-6, July 2026.
4
Good vibrations: Using VCTE to predict hepatic decompensation in MASLD
良好的振动：利用振动控制瞬时弹性成像（VCTE）预测MASLD患者的肝脏失代偿
Patel, Krishan S.; Arab, Juan Pablo
Hepatology. 84(1):7-8, July 2026.
Editorials（社论）
5
FIB-4 turns 20: A lesson of serendipity
FIB-4二十周年：一次 serendipity（意外发现）的启示
Sterling, Richard K.
Hepatology. 84(1):9-11, July 2026.
6
Cirrhotic portal vein thrombosis as a vascular rather than a thrombotic disorder
肝硬化门静脉血栓——一种血管性而非血栓性疾病
Huang, Xiaoquan; Lisman, Ton
Hepatology. 84(1):12-14, July 2026.
7
From sex to size: Rethinking fairness in liver transplantation
从性别到体型：重新思考肝移植中的公平性
Rosenthal, Benjamin E.; Serper, Marina
Hepatology. 84(1):15-16, July 2026.
8
Addressing the utility of a novel score for “at-risk” MASH in those with significant obesity
新型评分在显著肥胖人群中"高风险"代谢相关脂肪性肝炎（MASH）中的实用性探讨
Dillon, John F.; Leith, Damien; Brennan, Paul
Hepatology. 84(1):17-19, July 2026.
Original Articles（论著）
Liver Cancer（肝脏肿瘤）
9
Tumor site influences efficacy of MEKi and immunotherapy combinations in a preclinical model of cholangiocarcinoma
肿瘤部位影响MEKi联合免疫治疗在胆管癌临床前模型中的疗效
Hammons, Jacklyn N.; Warren, Emilie K.; Wittling, Megen C.; More
Hepatology. 84(1):20-36, July 2026.
10
RIPPLY1 suppresses cancer cell stemness via targeting TBX19 in CTNNB1-mutated hepatocellular carcinoma
RIPPLY1通过靶向TBX19抑制CTNNB1突变型肝细胞癌的肿瘤干细胞特性
Zhangyuan, Guangyan; Yu, Weiwei; Tian, Wenfang; More
Hepatology. 84(1):37-56, July 2026.
11
Anti-angiogenic therapy combined with immune checkpoint blockade mediates CCR7+CD8+ T-cell entry into HCC through high endothelial venules
抗血管生成治疗联合免疫检查点阻断通过高内皮微静脉促进CCR7+CD8+ T细胞进入HCC
Tang, Lu; Hou, Yingwen; Di, Tian; More
Hepatology. 84(1):57-73, July 2026.
Liver Pathobiology（肝脏病理生物学）
12
Hepatocyte-derived extracellular vesicles promote endothelial dedifferentiation in chronic liver disease through the miR-153-3p-pyroptosis axis
肝细胞来源的细胞外囊泡通过miR-153-3p-焦亡轴促进慢性肝病中的内皮去分化
Abad-Jordà, Laia; Andrés-Rozas, María; Martínez-Alcocer, Ana; More
Hepatology. 84(1):74-90, July 2026.
Liver Failure/Cirrhosis/Portal Hypertension（肝衰竭/肝硬化/门脉高压）
13
Endothelial-to-mesenchymal transition: A targetable mechanism that contributes to portal vein thrombosis in cirrhosis
内皮-间充质转化：肝硬化门静脉血栓中可靶向的关键机制
Anton, Aina; Shalaby, Sarah; Botero, María Luisa; More
Hepatology. 84(1):91-105, July 2026.
14
Sex and body size disparities under MELD 3.0: Evaluation of persisting gaps in liver transplant access
MELD 3.0下的性别与体型差异：肝移植可及性中持续存在的差距评估
Tanaka, Tomohiro; Shane, Dan M.; Lai, Jennifer C.
Hepatology. 84(1):106-116, July 2026.
Pediatrics（儿科学）
15
Serum bile acid levels predict the development of portal hypertension and high-risk esophageal varices following successful Kasai in biliary atresia
血清胆汁酸水平可预测胆道闭锁Kasai术后成功患者门脉高压及高风险食管静脉曲张的发生
Grimaud, Emilie; Gardin, Antoine; Ackermann, Oanez; More
Hepatology. 84(1):117-128, July 2026.
16
Reclassifying pediatric NAFLD using the steatotic liver disease framework: A multicenter retrospective study from the NASH CRN
利用脂肪性肝病框架重新分类儿童非酒精性脂肪性肝病（NAFLD）：来自NASH CRN的多中心回顾性研究
Lam, Tin Bo Nicholas; Yates, Katherine P.; Noon, Sheila L.; More
Hepatology. 84(1):129-142, July 2026.
Steatohepatitis（脂肪性肝炎）
17
KLF9 drives intermittent hypoxia-induced MASLD by suppressing the NR4A1–p38 MAPK hepatic metabolic axis
KLF9通过抑制NR4A1–p38 MAPK肝脏代谢轴驱动间歇性缺氧诱导的MASLD
Hua, Hongting; Wang, Dong; He, Lanqiaofeng; More
Hepatology. 84(1):143-160, July 2026.
18
Global performance of non-invasive tests in MASLD: Insights from the G-MASLD study
MASLD无创检测的全球表现：来自G-MASLD研究的洞察
Younossi, Zobair M.; de Avila, Leyla; Petta, Salvatore; More
Hepatology. 84(1):161-174, July 2026.
19
Head-to-head comparison between vibration-controlled transient elastography and histology in predicting liver-related events due to metabolic dysfunction-associated steatotic liver disease
振动控制瞬时弹性成像与组织学在预测代谢功能障碍相关脂肪性肝病肝脏相关事件中的头对头比较
Zhang, Yangyue; Lee, Hye Won; Lin, Huapeng; More
Hepatology. 84(1):175-190, July 2026.
20
Development and validation of a noninvasive score for at-risk metabolic dysfunction–associated steatohepatitis in individuals with obesity undergoing bariatric surgery
针对肥胖减重手术人群中"高风险"代谢功能障碍相关脂肪性肝炎的无创评分的开发与验证
Huang, Xin; Zhu, Tao; Li, Shumin; More
Hepatology. 84(1):191-203, July 2026.
Original Articles（论著）
Steatohepatitis（脂肪性肝病）
21
Predictors of fibrosis, clinical events, and mortality in MASLD: Data from the Global-MASLD study
MASLD中纤维化、临床事件及死亡率的预测因素：来自Global-MASLD研究的数据
Younossi, Zobair M.; de Avila, Leyla; Petta, Salvatore; More
Hepatology. 84(1):204-215, July 2026.
Viral Hepatitis（病毒性肝炎）
22
HBV induces liver fibrosis through the generation of reactive oxygen species in a pyruvate-dependent manner
乙肝病毒（HBV）以丙酮酸依赖方式通过活性氧生成诱导肝纤维化
Duan, Xiaoqiong; Li, Shasha; Li, Qingyuan; More
Hepatology. 84(1):216-232, July 2026.
23
IL1β signaling mediates the interaction between hepatitis B and C viruses
IL1β信号介导乙型与丙型肝炎病毒之间的相互作用
Zhang, Fan; Zhao, Yuanyuan; Bian, Lu; More
Hepatology. 84(1):233-250, July 2026.
Reviews（综述）
24
Reprogramming macrophages to treat liver diseases
巨噬细胞重编码治疗肝脏疾病
Simón-Codina, Blanca; Cacho-Pujol, Júlia; Moles, Anna; More
Hepatology. 84(1):251-272, July 2026.
25
Mechanisms coupling lipid droplets to MASLD pathophysiology
脂滴与MASLD病理生理偶联的机制
Reid, Mari V.; Fredickson, Gavin; Mashek, Douglas G.
Hepatology. 84(1):273-291, July 2026.
26
Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic
新一代抗病毒药物与肥胖流行时代的肝癌预防
Suzuki, Hiroyuki; Fujiwara, Naoto; Singal, Amit G.; More
Hepatology. 84(1):292-320, July 2026.
Special Article（专题论著）
27
Non-invasive tests: Establishing efficacy for metabolic dysfunction–associated steatohepatitis beyond the biopsy—Current perspectives from the Division of Hepatology and Nutrition, US Food and Drug Administration
无创检测：在超越活检的层面确立代谢功能障碍相关脂肪性肝炎的有效性——来自美国食品药品监督管理局肝病与营养部的当前观点
Anania, Frank A.; Hager, Rebecca; Higgins, Karen; More
Hepatology. 84(1):321-327, July 2026.
Correspondence（读者来信）
28
Letter to the Editor: Re-evaluating the clinical relevance of the RIPPLY1-TBX19 axis in CTNNB1-mutant hepatocellular carcinoma
致编辑信：重新评估RIPPLY1-TBX19轴在CTNNB1突变型肝细胞癌中的临床相关性
Zhang, Xiang; Gong, Hui; Gu, Kaikai; More
Hepatology. 84(1):E1-E2, July 2026.
29
Letter to the Editor: Nuances in POCUS-guided hemodynamic assessment in cirrhosis
致编辑信：POCUS引导下肝硬化血流动力学评估中的细微之处
Koratala, Abhilash; Argaiz, Eduardo R.
Hepatology. 84(1):E3-E4, July 2026.
30
Reply: Nuances in POCUS-guided hemodynamic assessment in cirrhosis
回复：POCUS引导下肝硬化血流动力学评估中的细微之处
Premkumar, Madhumita; Kajal, Kamal
Hepatology. 84(1):E5-E6, July 2026.
31
Letter to the Editor: The PNPLA3 paradox—Does genotype modify the clinical utility of the MASLD framework in children?
致编辑信：PNPLA3悖论——基因型是否改变MASLD框架在儿童中的临床实用性？
Liu, Boyan; Li, Heran
Hepatology. 84(1):E7-E8, July 2026.
32
Reply: The PNPLA3 paradox—Does genotype modify the clinical utility of the MASLD framework in children?
回复：PNPLA3悖论——基因型是否改变MASLD框架在儿童中的临床实用性？
Lam, Tin Bo Nicholas; Goyal, Nidhi P.; Newton, Kimberly P.; More
Hepatology. 84(1):E9-E10, July 2026.
33
Letter to the Editor: The profile of HBsAg levels after nucleos(t)ide analogues treatment is crucial for achieving a functional cure
致编辑信：核苷（酸）类似物治疗后HBsAg水平的变化特征对实现功能性治愈至关重要
Tang, Qiao; Hu, Peng
Hepatology. 84(1):E11-E12, July 2026.
34
Letter to the Editor: Comments on the Study—Body size disparities limit women’s access to liver transplantation under the MELD 3.0 scoring system
致编辑信：对"体型差异限制女性在MELD 3.0评分体系下获得肝移植机会"研究的评论
He, Jiahang; Xie, Qing; Cao, Zhujun
Hepatology. 84(1):E13, July 2026.
35
Letter to the Editor: Clarifying validation and statistical aspects of AI-based risk prediction in liver disease
致编辑信：澄清AI基于风险预测在肝病中的验证与统计学问题
Liu, Jing; Zhang, Guo-Ming
Hepatology. 84(1):E14-E15, July 2026.
36
Reply: Clarifying validation and statistical aspects of AI-based risk prediction in liver disease
回复：澄清AI基于风险预测在肝病中的验证与统计学问题
Zhang, Peng; Su, Grace L.
Hepatology. 84(1):E16-E17, July 2026.
37
Letter to the Editor: Clarifying endothelial specificity and hemodynamic coupling of the miR-153-3p–pyroptosis axis
致编辑信：澄清miR-153-3p–焦亡轴的内皮特异性与血流动力学偶联
Weng, Dandan
Hepatology. 84(1):E18-E19, July 2026.
38
Letter to the Editor: Placebo drift, dose heterogeneity, and the winner’s curse—Re-evaluating the hierarchy of MASH therapeutics
致编辑信：安慰剂漂移、剂量异质性与赢者诅咒——重新评估MASH治疗药物的层级
Philips, Cyriac Abby; Oommen, Tharun Tom; Ahamed, Rizwan
Hepatology. 84(1):E20-E21, July 2026.
39
Reply: Placebo drift, dose heterogeneity, and the winner’s curse—Re-evaluating the hierarchy of MASH therapeutics
回复：安慰剂漂移、剂量异质性与赢者诅咒——重新评估MASH治疗药物的层级
Souza, Matheus; Huang, Daniel Q.; Loomba, Rohit
Hepatology. 84(1):E22-E23, July 2026.
40
Letter to the Editor: Interpreting the clinical decision value of glycomic-based models for early HCC detection in CHB
致编辑信：解读糖组学模型在CHB早期HCC检测中的临床决策价值
Jiang, Qing-Bao; Zhang, Guo-Ming
Hepatology. 84(1):E24-E25, July 2026.
41
Letter to the Editor: From weight to waist—Refining fibrosis prediction in the Global MASLD cohort
致编辑信：从体重到腰围——优化Global MASLD队列中的纤维化预测
Zeng, Hong; Huang, Xi
Hepatology. 84(1):E26-E27, July 2026.
42
Reply: From weight to waist—Refining fibrosis prediction in the Global MASLD cohort
回复：从体重到腰围——优化Global MASLD队列中的纤维化预测
Stepanova, Maria; Younossi, Zobair M.
Hepatology. 84(1):E28-E29, July 2026.
Hepatology[Jour] AND 84[volume] AND 2[issue]
肝脏病学 84卷2期
https://journals.lww.com/hep/pages/currenttoc.aspx
Hepatology Highlights（肝病学亮点）
1
PSC’s itch is worth scratching: Pruritus can be more than a symptom
原发性硬化性胆管炎瘙痒值得重视：瘙痒并非单纯伴随症状
Yigit Yazarkan
Hepatology. August 2026: 84(2):329-330
2
The weight of progress: Why dynamic weight trajectories matter in MASLD
体重变化的临床意义：代谢相关脂肪性肝病中动态体重轨迹的价值
Guneet Sidhu
Hepatology. August 2026: 84(2):331-332
3
The liver joins the CKM conversation: Fibrosis risk across the cardiometabolic spectrum
肝脏纳入心脏代谢疾病评估：横跨心脏代谢疾病谱的肝纤维化风险
Omar Albhaisi, Juan Pablo Arab
Hepatology. August 2026: 84(2):333-334
4
Pizza versus Pi*ZZ: The metabolic amplifiers in alpha-1 antitrypsin deficiency
饮食与基因交互：α1-抗胰蛋白酶缺乏症的代谢放大因素
John Grady, Juan Pablo Arab
Hepatology. August 2026: 84(2):335-336
Editorials（社论）
5
Stains in primary biliary cholangitis: Untangling promise from bias
原发性胆汁性胆管炎相关染色标志物：区分临床价值与研究偏倚
Therese Bittermann, Charles E. Leonard
Hepatology. August 2026: 84(2):337-339
6
Multiomics and machine learning in cholangiocarcinoma: A paradigm shift toward molecular subtyping and precision therapy
多组学与机器学习在胆管癌中的应用：迈向分子分型与精准治疗的范式革新
Meng Xu, Ju-Seog Lee
Hepatology. August 2026: 84(2):340-342
7
A targeted liver cancer therapy independent of immune checkpoint block
不依赖免疫检查点抑制剂的肝癌靶向治疗方案
Bangyan L. Stiles
Hepatology. August 2026: 84(2):343-345
8
Alcohol use dominates determining liver-related events in steatotic liver disease: Rethinking the role of metabolic dysfunction
饮酒是脂肪性肝病肝脏不良事件的核心诱因：重新审视代谢功能障碍的作用
Luis Antonio Díaz, Winston Dunn, Ashwani K. Singal
Hepatology. August 2026: 84(2):346-348
9
Shedding new light on the chicken-and-egg dilemma of hepatitis delta virus (HDV) replication initiation
厘清丁型肝炎病毒复制起始的因果先后难题
Julie Lucifora, Francesco Negro
Hepatology. August 2026: 84(2):349-352
Original Articles: Immune-Mediated Diseases, DILI, and Biliary Tract Disease（论著：免疫介导性肝病、药物性肝损伤与胆道疾病）
10
Pruritus is common in primary sclerosing cholangitis, persists over time, and its intensity is associated with disease severity: a multicentre, prospective observational study
原发性硬化性胆管炎瘙痒高发且持续存在，瘙痒程度与疾病严重度相关：一项多中心前瞻性观察研究
Nasir Hussain, Rodrigo V. Motta, Usha Gungabissoon, Linda Casillas, Sumanta Mukherjee, Andrea Ribeiro, Megan M. Mclaughlin, Kaitlin Hagan, Khushpreet Bhandal, Penelope Rogers, Martine Walmsley, James Ferguson, Andreas E. Kremer, Emma L. Culver, Palak J. Trivedi
Hepatology. August 2026: 84(2):353-366
11
Association between statin use and hepatic decompensation in patients with primary biliary cholangitis: A target trial emulation study
他汀类药物使用与原发性胆汁性胆管炎患者肝失代偿的关联：模拟目标临床试验研究
Jonggi Choi, Junqing Xu, Vy H. Nguyen, Eric Przybyszewski, Daniel S. Pratt, Jiunn Song, Allison Carroll, Megan Michta, Erik Almazan, Tracey G. Simon, Raymond T. Chung
Hepatology. August 2026: 84(2):367-377
Original Articles: Liver Cancer（论著：肝脏肿瘤）
12
NEK7-induced phosphorylation of EGFR on serine 1070 drives the acquired lenvatinib resistance in hepatocellular carcinoma
NEK7介导EGFR第1070位丝氨酸磷酸化诱发肝细胞癌的仑伐替尼获得性耐药
Qibo Huang, Weijian Wang, Qianyun Ge, Dafeng Xu, Renshun Dong, Ruizhi Chang, Xing Wu, Jie Mo, Chen Su, Deng Ning, Qiumeng Liu, Huifang Liang, Guihua Wang, Jin Chen, Xifeng Fu, Xiaoping Chen, Junnan Liang, Bixiang Zhang
Hepatology. August 2026: 84(2):378-395
13
Multiomics combined with machine learning defines unique molecular subtypes of cholangiocarcinoma and identifies TNK1 as a therapeutic target
多组学联合机器学习鉴定胆管癌独特分子亚型并筛选TNK1为治疗靶点
Dong-Gi Mun, Erik Jessen, Jennifer L. Tomlinson, Danielle Carlson, Rohit Budhraja, Roberto Alva-Ruiz, Amro Abdelrahman, Ryan Watkins, Lindsey Gregory, Chantal McCabe, Chen Wang, Rondell P. Graham, Kathryn Woods, Martin Golkowski, Marshall Baker, Gregory J. Gores, Sumera I. Ilyas, Caitlin Conboy, Ellen L. Larson, Jack W. Sample, Enis H. Ozmert, Richard K. Kandasamy, Mitesh J. Borad, Lewis Roberts, Joshua Andersen, Akhilesh Pandey, Rory L. Smoot
Hepatology. August 2026: 84(2):396-410
14
Distinct gut microbiota but common metabolomic signatures between viral and MASLD HCC contribute to outcomes of combination immunotherapy
病毒性与代谢相关脂肪性肝病相关肝癌肠道菌群存在差异，但代谢组特征趋同，共同影响联合免疫治疗疗效
Pei-Chang Lee, Chi-Jung Wu, Ya-Wen Hung, Chieh-Ju Lee, Hsien-Chen Mon, Chen-Ta Chi, I-Cheng Lee, Yu-Lun Kuo, Shih-Hsuan Chou, Jiing-Chyuan Luo, Ming-Chih Hou, Yi-Hsiang Huang
Hepatology. August 2026: 84(2):411-423
15
Efficacious suppression of primary and metastasized liver tumors by polyIC-loaded lipid nanoparticles
载聚肌胞苷酸脂质纳米颗粒可有效抑制肝脏原发及转移性肿瘤
Yingluo Liu, Xinyi Wang, Nishta Krishnan, Timothy Hsiao, Yichun Ji, Kota Kaneko, Marcos G. Teneche, Peter D. Adams, Elina Zuniga, Susan M. Kaech, Liangfang Zhang, Gen-Sheng Feng
Hepatology. August 2026: 84(2):424-439
16
Genomic and transcriptomic profiling of hepatocellular carcinoma in patients with Fontan-associated liver disease
丰坦手术相关性肝病合并肝细胞癌的基因组与转录组图谱分析
Taiji Yamazoe, Eiji Kakazu, Michitaka Matsuda, Masaaki Mino, Taizo Mori, Sachiyo Yoshio, Yuriko Tsutsui, Takashi Motomura, Shinji Itoh, Koichiro Haruki, Kenei Furukawa, Shinichiro Yamada, Takeshi Takamoto, Takehiro Noda, Hidetoshi Eguchi, Kiyoshi Hasegawa, Yuji Morine, Toru Ikegami, Tomoharu Yoshizumi, Tatsuya Kanto
Hepatology. August 2026: 84(2):440-452
17
Deep learning-assisted tumor radiomic dynamics on MRI predict pathological complete response in HCC undergoing immune-based therapy followed by hepatectomy
深度学习辅助MRI肿瘤影像组学动态特征预测免疫治疗联合肝切除肝细胞癌患者的病理完全缓解
Shi-Qi Zhou, Lu-Na Wang, Li-Fang Wu, Li-Yu Sun, Yu-Chen Yang, Zi-Yue Yang, Zi-Yi Wang, Tian He, Fei Li, Ling-Li Chen, Hui Li, Xiao-Dong Zhu, Ying-Hao Shen, Cheng Huang, Yuan Ji, Qiang Gao, Jian Zhou, Jia Fan, Yong-Jun Chen, Tian-Qiang Song, Bin Xu, Hui-Chuan Sun
Hepatology. August 2026: 84(2):453-468
Original Articles: Liver Pathobiology（论著：肝脏病理生物学）
18
Epigenetic repression of hepatocyte FoxO1 disrupts local immune homeostasis and promotes liver inflammation
肝细胞FoxO1表观遗传抑制破坏肝脏局部免疫稳态并诱发肝炎症
Zhigang Lei, Yu Wu, Weijie Xue, Dongmei Zhu, Junyao Shen, Chenxu Mao, Ziling Wang, Chuanhong Huang, Yuxin Zhang, Jifeng Zhu, Lei Xu, Yalin Li, Xiujun Zhang, Shouguo Liu, Xiaojun Chen, Chunyan Ye, Sha Zhou, Chuan Su
Hepatology. August 2026: 84(2):469-486
19
CXCR6 defines a distinct resident state in γδ T cells for protecting from liver cirrhosis
CXCR6标记具有独特定居表型的γδT细胞，可抵御肝硬化进展
Jiahao Ji, Zhitao Chen, Wenjing He, Yanxu Chen, Dongmei Ye, Yingqian Zhong, Xiaomin Shi, Xiaojun Ouyang, Zhimin Zeng, Qianyu Ye, Xiaoshun He, Zhinan Yin, Jianlei Hao, Yifang Gao
Hepatology. August 2026: 84(2):487-502
Original Articles: Steatohepatitis（论著：脂肪性肝炎）
20
Differential associations of cardiometabolic risk factors with liver-related events by alcohol consumption category: Results from a large population-based study
不同饮酒分层下心代谢危险因素与肝脏不良事件的差异性关联：一项大样本人群研究
Hongliang Xue, Liqing Wang, Yuankai Wu, Yingxin Liao, Shijia Wang, Ailan Chen, Sun On Chan, Wenhua Ling, Xu Chen, Chao Yu
Hepatology. August 2026: 84(2):503-513
21
Association between longitudinal weight change and clinical outcome in individuals with MASLD
代谢相关脂肪性肝病患者纵向体重变化与临床预后的相关性
Yu Shi, Ruoqi Zhou, Seung Up Kim, Terry Cheuk-Fung Yip, Emmanuel Tsochatzis, Salvatore Petta, Atsushi Nakajima, Hannes Hagström, Elisabetta Bugianesi, Wah-Kheong Chan, Jérôme Boursier, Boon-Bee George Goh, Arun J. Sanyal, Manuel Romero-Gomez, José Luis Calleja, Victor de Lédinghen, Philip Noel Newsome, Jian-Gao Fan, Michelle Lai, Laurent Castéra, Céline Fournier-Poizat, Hye Won Lee, Grace Lai-Hung Wong, Grazia Pennisi, Masato Yoneda, Ying Shang, Angelo Armandi, Marc de Saint-Loup, Clemence M. Canivet, Kevin Kim-Jun Teh, Amon Asgharpour, Rocio Gallego-Durán, Elba Llop, Carmen Lara-Romero, Mandy Sau-Wai Chan, Mirko Zoncape, Huapeng Lin, Wen-Yue Liu, Giovanni Targher, Christopher D. Byrne, Vincent Wai-Sun Wong, Ming-Hua Zheng,
Hepatology. August 2026: 84(2):514-528
22
Cardiovascular–kidney–metabolic syndrome and the risk of liver fibrosis progression and liver-related events in MASLD
心肾代谢综合征与代谢相关脂肪性肝病肝纤维化进展及肝脏不良事件风险的关联
Xiao-Dong Zhou, Qin-Fen Chen, Qiong-Yue Fan, Seung Up Kim, Terry Cheuk-Fung Yip, Salvatore Petta, Atsushi Nakajima, Emmanuel Tsochatzis, Jérôme Boursier, Elisabetta Bugianesi, Hannes Hagström, Wah-Kheong Chan, Manuel Romero-Gomez, José Luis Calleja, Victor de Lédinghen, Laurent Castéra, Arun J. Sanyal, George Boon-Bee Goh, Philip Noel Newsome, Jian-Gao Fan, Michelle Lai, Céline Fournier-Poizat, Hye Won Lee, Grace Lai-Hung Wong, Angelo Armandi, Ying Shang, Grazia Pennisi, Elba Llop, Masato Yoneda, Marc de Saint-Loup, Clemence M. Canivet, Paloma Carrillo-Fernandez, Carmen Lara-Romero, Rocio Gallego-Durán, Amon Asgharpour, Kevin Kim-Jun Teh, Mandy Sau-Wai Chan, Huapeng Lin, Wen-Yue Liu, Giovanni Targher, Christopher D. Byrne, Vincent Wai-Sun Wong, Ming-Hua Zheng,
Hepatology. August 2026: 84(2):529-541
23
Amplification of genetic and metabolic factors in alpha-1 antitrypsin deficiency
α1-抗胰蛋白酶缺乏症中遗传与代谢危险因素的协同放大效应
Christina Schrader, Malin Fromme, Paul Ellis, Audrey Payancé, Mattias Mandorfer, Jan Stolk, Bart van Hoek, Katrine H. Thorhauge, Monica Pons, Marc Miravitlles, Guido Stirnimann, Sona Frankova, Jan Sperl, Andreas E. Kremer, Katharina Remih, Emily K. Weber, Lorenz Balcar, Annelot D. Sark, Benedikt Schaefer, Joanna Chorostowska-Wynimko, Elmar Aigner, Sophie Gensluckner, Heike Bantel, Jef Verbeek, Zoe Mariño, Rohit Loomba, Heinz Zoller, Michael Trauner, Joan Genesca, Virginia Clark, Aleksander Krag, Noel G. McElvaney, William J. Griffiths, Alice M. Turner, Pavel Strnad
Hepatology. August 2026: 84(2):542-558
Original Articles: Viral Hepatitis（论著：病毒性肝炎）
24
CDK8 and CDK19 Mediator kinases are required for hepatitis delta virus replication
中介激酶CDK8与CDK19是丁型肝炎病毒复制的必需分子
Angga Prawira, Mattis Hilleke, Mengqian Chen, Igor B. Roninson, Ralf Bartenschlager, Stephan Urban, Yi Ni
Hepatology. August 2026: 84(2):559-572
Reviews（综述）
25
Unmet needs in diagnosis and management of portopulmonary hypertension: How far have we reached?
门脉性肺动脉高压诊疗尚未满足的临床需求：当前研究进展综述
Michael J. Krowka, Hilary M. DuBrock, Sarah Raevens, Michael B. Fallon
Hepatology. August 2026: 84(2):573-581
26
Getting to HBV cure—Will new biomarkers help?
迈向乙型肝炎治愈：新型生物标志物能否提供助力？
Jordan J. Feld, Adam J. Gehring, Fabien Zoulim
Hepatology. August 2026: 84(2):582-600
Special Articles（专题论著）
27
A multisociety consensus statement on a new common definition and diagnostic criteria for PSVD or NCPF
多学会关于门窦血管病变/非肝硬化性门脉高压新统一定义与诊断标准的共识声明
Virginia Hernandez-Gea, Valerie Paradis, Maha Guindi, Venancio A.F. Alves, Amal Aqul, Eira Cerda, Sarwa Darwish Murad, Prasenjit Das, Angelo Di Giorgio, Luiz A.R. de Freitas, Tassos Grammatikopoulos, Kenichi Harada, Nelia Hernandez, Samar H. Ibrahim, Sanjay Kakar, Saul Karpen, David E. Kleiner, Necati Ormeci, Xiaolong Qi, Puja Sakhuja, Maria Isabel Schinoni, Romil Saxena, Alexandre Sayadi, Akash Shukla, Dina G. Tiniakos, Elizabeth Verna, Kerry Wong, Laure Elkrief, Christine Sempoux, Theo Heller, Pierre-Emmanuel Rautou
Hepatology. August 2026: 84(2):601-616
28
Consistent efficacy of efruxifermin across PNPLA3 genotypes in phase 2b trials in MASH
Ⅱb期临床试验证实依鲁西佛明在不同PNPLA3基因型代谢相关脂肪性肝炎人群中疗效稳定
Naga Chalasani, Erik J. Tillman, Sonja K. Billes, Timothy Rolph, Mazen Noureddin
Hepatology. August 2026: 84(2):617-620
Correspondence（通信）
29
Letter to the Editor: Is fecal acetate a viable pan-etiological predictor of outcomes in HCC immunotherapy?
致编者信：粪便乙酸盐是否可作为全病因肝癌免疫治疗疗效预测标志物？
Zhou Zhao, Jian Sun, Qiuhong You, Zhixian Lan, Yinghong Zhu
Hepatology. August 2026: 84(2):E30-E31
30
Reply: Is fecal acetate a viable pan-etiological predictor of outcomes in HCC immunotherapy?
回复：粪便乙酸盐是否可作为全病因肝癌免疫治疗疗效预测标志物？
Pei-Chang Lee, Yi-Hsiang Huang
Hepatology. August 2026: 84(2):E32-E33
31
Letter to the Editor: Survival analysis pitfalls in MASLD: Proportional hazards, immortal time, and follow-up discrepancies
致编者信：代谢相关脂肪性肝病生存分析常见误区：比例风险、永生时间与随访偏差
Jian Huang
Hepatology. August 2026: 84(2):E34-E35
32
Reply: Survival analysis pitfalls in MASLD—Proportional hazards, immortal time, and follow-up discrepancies
回复：代谢相关脂肪性肝病生存分析常见误区——比例风险、永生时间与随访偏差
Yu Shi, Ruoqi Zhou, Yuanjie Pang, Vincent Wai-Sun Wong, Ming-Hua Zheng
Hepatology. August 2026: 84(2):E36-E37
33
Letter to the Editor: Beyond Semantics—Acknowledging diagnostic differences between NAFLD and MASLD
致编者信：不止命名差异——正视NAFLD与MASLD的诊断区分要点
Giovani Schulte Farina, Jonathan Soldera
Hepatology. August 2026: 84(2):E38-E39
34
Reply: Beyond semantics—Acknowledging diagnostic differences between NAFLD and MASLD
回复：不止命名差异——正视NAFLD与MASLD的诊断区分要点
Madalina-Gabriela Indre, Federico Ravaioli
Hepatology. August 2026: 84(2):E40-E41
35
Letter to the editor: Deep learning and digital pathology for HCC prediction in steatotic liver disease
致编者信：深度学习与数字病理用于脂肪性肝病肝癌发生风险预测
Luisa Giudice, Stefano Granieri, Stefania Galassi, Sante De Santis, Emmanuel Pio Pastore
Hepatology. August 2026: 84(2):E42-E43
36
Reply: Deep learning and digital pathology power prediction of HCC development in steatotic liver disease
回复：深度学习联合数字病理可精准预测脂肪性肝病患者肝癌发病风险
Takuma Nakatsuka, Ryosuke Tateishi, Masaya Sato, Kazuhiko Koike
Hepatology. August 2026: 84(2):E44-E45
Errata（勘误）
37
Erratum: Reciprocal regulation between forkhead box M1/NF-κB and methionine adenosyltransferase 1A drives liver cancer
勘误：FOXM1/NF-κB与甲硫氨酸腺苷转移酶1A相互调控促进肝癌发生
Yuan Li, Liqing Lu, Jian Tu, Jing Zhang, Ting Xiong, Wei Fan, Jiaohong Wang, Meng Li, Yibu Chen, Justin Steggerda, Hui Peng, Yongheng Chen, Tony WH Li, Zhi-Gang Zhou, José M Mato, Ekihiro Seki, Ting Liu, Heping Yang, Shelly C. Lu
Hepatology. August 2026: 84(2):E46-E47
38
Erratum: AlphaB-crystallin complexes with 14-3-3zeta to induce epithelial-mesenchymal transition and resistance to sorafenib in hepatocellular carcinoma
勘误：αB-晶状体蛋白结合14-3-3ζ诱导肝细胞癌上皮间质转化与索拉非尼耐药
Huang Xiao-Yong, Ke Ai-Wu, Shi Guo-Ming, Zhang Xin, Zhang Chi, Shi Ying-Hong, Wang Xiao-Ying, Ding Zhen-Bin, Xiao Yong-Sheng, Yan Jun, Qiu Shuang-Jian, Fan Jia, Zhou Jian
Hepatology. August 2026: 84(2):E48-E49
39
Erratum: AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis
勘误：美国肝病研究协会慢加急性肝衰竭与重症肝硬化患者管理临床实践指南
Constantine J. Karvellas, Jasmohan S. Bajaj, Patrick S. Kamath, Lena Napolitano, Jacqueline G. O’Leary, Elsa Solà, Ram Subramanian, Florence Wong, Sumeet K. Asrani
Hepatology. August 2026: 84(2):E50-E50
40
Erratum: Noninvasive assessment of liver disease severity in NAFLD and T2D
勘误：非侵入性评估非酒精性脂肪性肝病合并2型糖尿病患者肝病严重程度
Grazia Pennisi, Marco Enea, Vincenzo Falco, Guruprasad P. Aithal, Naaventhan Palaniyappan, Yusuf Yilmaz, Jerome Boursier, Christophe Cassinotto, Victor de Lédinghen, Wah Kheong Chan, Sanjiv Mahadeva, Peter Eddowes, Philip Newsome, Thomas Karlas, Johannes Wiegand, Vincent Wai-Sun Wong, Jörn M. Schattenberg, Christian Labenz, Won Kim, Myoung Seok Lee, Monica Lupsor-Platon, Jeremy F. Cobbold, Jian-Gao Fan, Feng Shen, Katharina Staufer, Michael Trauner, Rudolf Stauber, Atsushi Nakajima, Masato Yoneda, Elisabetta Bugianesi, Ramy Younes, Silvia Gaia, Ming-Hua Zheng, Calogero Cammà, Quentin M. Anstee, Ferenc E. Mózes, Michael Pavlides, Salvatore Petta
Hepatology. August 2026: 84(2):E51-E51
Retraction（撤稿声明）
41
Retraction: HSP72 interacts with PRDX6 to deubiquitinate mitochondrial PINK1, activating mitophagy to treat MASLD
撤稿声明：热休克蛋白72结合过氧化物还原蛋白6去泛素化线粒体PINK1，激活线粒体自噬改善代谢相关脂肪性肝病
Yong Rao, Rui Su, Wen-jie Cao, Yue Chen, Shu-heng Huang, Jun-jie Wu, Darren C. Henstridge, Lin-sheng Huang, Jin Liu, Fei-fei Liu, Zhong-ping Jiang, Cong-jun Xu, Zhi-shu Huang, Ji-ming Ye, Ling Huang
Hepatology. August 2026: 84(2):E52-E52
Hepatology[Jour] AND 84[volume] AND 3[issue]
肝脏病学 84卷3期
https://journals.lww.com/hep/pages/currenttoc.aspx
Hepatology Highlights（《肝脏病学》重点导读）
1
The road less traveled: Mapping the complex trajectories of PSC‑IBD
少有人走的路：原发性硬化性胆管炎‑炎症性肠病复杂病程轨迹解析
Mian B. Khalid
Hepatology. September 2026: 84(3):621‑622
2
One cancer, four personalities: Transcriptomic signatures reveal molecular subtypes of advanced biliary tract cancer
一种肿瘤，四种表型：转录组特征揭示晚期胆道癌分子亚型
Muhammed Dogukan Aksu
Hepatology. September 2026: 84(3):623‑624
3
Hepatic footprint of emerging antihyperglycemic therapies
新型降糖治疗的肝脏效应
P. Vineeth Daniel
Hepatology. September 2026: 84(3):625‑626
4
No prescription needed: Remote nutrition care linked to fewer liver events
无需处方：远程营养干预可减少肝脏相关不良事件
Leandro Sierra, Juan Pablo Arab
Hepatology. September 2026: 84(3):627‑628
Fellows' Corner（青年学者园地）
5
Fellows’ Corner
青年学者园地
Somaya Albhaisi
Hepatology. September 2026: 84(3):629‑630
Editorials（社论）
6
Population‑level screening for liver disease: Opportunities and challenges
人群水平肝脏疾病筛查：机遇与挑战
Pedro Ochoa‑Allemant, Marina Serper
Hepatology. September 2026: 84(3):631‑633
7
Two decades of hepatitis E in solid organ transplantation: From endemic insight to unresolved therapeutic questions
实体器官移植中戊型肝炎二十年：从流行特征到尚未解决的治疗难题
Patrick Behrendt, Christoph Neumann‑Haefelin
Hepatology. September 2026: 84(3):634‑637
8
Interpreting surgical associations in primary sclerosing cholangitis: Caution in clinical messaging
解读原发性硬化性胆管炎的手术相关性：临床解读需审慎
Bregje Mol, Palak J. Trivedi
Hepatology. September 2026: 84(3):638‑640
Original Articles: Immune‑Mediated Diseases, DILI, and Biliary Tract Disease（论著：免疫介导性疾病、药物性肝损伤与胆道疾病）
9
Statins halt polycystic liver disease by reprogramming metabolism and normalizing mitochondrial bioenergetics in cystic cholangiocytes
他汀类药物通过重编程囊胆管上皮细胞代谢、恢复线粒体生物能量功能抑制多囊肝进展
Enara Markaide, Laura Izquierdo‑Sanchez, Irene Olaizola, Josu Urretabizkaia‑Garmendia, Mikel Ruiz de Gauna, Xabier Buqué, Irune Lasa‑Elosegi, Ainhoa Lapitz, Thomas Bais, Beatriz Val, Pedro M. Rodrigues, Rui E. Castro, Maria J. Perugorria, Luis Bujanda, Ron Gansevoort, Joost P.H. Drenth, Patricia Aspichueta, Jesus M. Banales
Hepatology. September 2026: 84(3):641‑657
10
Understanding hepatopancreatobiliary cancer risks in a population‑based primary sclerosing cholangitis–inflammatory bowel disease cohort
基于人群的原发性硬化性胆管炎‑炎症性肠病队列肝胆胰肿瘤风险研究
Kristel K. Leung, Wenbin Li, Bettina Hansen, Aliya Gulamhusein, Lauren Lapointe‑Shaw, Amanda Ricciuto, Eric I. Benchimol, Jennifer A. Flemming, Gideon M. Hirschfield
Hepatology. September 2026: 84(3):658‑671
Original Articles: Liver Cancer（论著：肝脏肿瘤）
11
GPC3‑based circular RNA vaccine suppresses hepatocellular carcinoma progression by activating adaptive immune responses
基于GPC3的环状RNA疫苗通过激活适应性免疫应答抑制肝细胞癌进展
Yifan Jiang, Yu Li, Tong Wu, Linping Cao, Guangming Xu, Jiwei Liu, Chenguang Hua, Chaofeng Ding, Beng Yang, Rongliang Tong, Diyu Chen, Jian Wu
Hepatology. September 2026: 84(3):672‑689
12
Laser‑activated nanoparticles rewire tumor microenvironment enhancing PD‑1 blockade and T cell response in cholangiocarcinoma
激光激活纳米颗粒重编程肿瘤微环境增强胆管癌PD‑1阻断疗效与T细胞应答
Mirko Minini, Giulio Avveduto, Sonia Becharef, Marie Meunier‑Thaens, Bouchra Lekbaby, Maria Perez‑Lazon, Alice Machado, Thomas Guilbert, Julie Lesieur, Gilles Renault, Sara Ceccacci, Ida Chiara Guerrera, Christophe Klein, Jérémy Augustin, Rana Bazzi, Stephane Roux, Jonathan Pol, Emmanuel Donnadieu, Florence Gazeau, Laura Fouassier
Hepatology. September 2026: 84(3):690‑707
13
FXR splicing by SF3B3 promotes MYC‑driven hepatocarcinogenesis
SF3B3介导FXR可变剪接促进MYC驱动的肝细胞癌发生
Xue Wang, Jiahua Luo, Lifeng Han, Tong Xu, Haichuan Wang, Mingzhe Zhang, Gen Li, Xichuan Li, Weihua Zhang, Youcai Zhang
Hepatology. September 2026: 84(3):708‑725
14
Biology‑driven stratification of advanced biliary tract cancer treated with nab‑paclitaxel plus gemcitabine–cisplatin: A prospective observational cohort study
白蛋白结合型紫杉醇联合吉西他滨‑顺铂治疗晚期胆道癌的生物学分层：一项前瞻性观察队列研究
Seonjeong Woo, Beodeul Kang, Sung Hwan Lee, Jung Sun Kim, Haeyoun Kang, Seok Jeong Yang, Chansik An, Gwangil Kim, Gae Hoon Jo, Chang‑Il Kwon, Min Je Sung, Suk Pyo Shin, Sanghoon Jung, Sohyun Hwang, Chan Kim, Hong Jae Chon
Hepatology. September 2026: 84(3):726‑739
15
Satellite lesions versus intrahepatic metastasis in multifocal intrahepatic cholangiocarcinoma: Prognostic impact and genomic profiling
多灶性肝内胆管癌卫星灶与肝内转移：预后价值及基因组特征分析
Tao Wei, Zhi‑Jie Ma, Shouliang Guo, Matthew Weiss, Irinel Popescu, Hugo P. Marques, Luca Aldrighetti, Shishir K. Maithel, Carlo Pulitano, Todd W. Bauer, Feng Shen, George A. Poultsides, Oliver Soubrane, Guillaume Martel, Bas Groot Koerkamp, Itaru Endo, Tingbo Liang, Yi Lyu, Timothy M. Pawlik, Xu‑Feng Zhang,
Hepatology. September 2026: 84(3):740‑755
16
Long‑term outcomes of atezolizumab–bevacizumab in unresectable hepatocellular carcinoma: A real‑world study
阿替利珠单抗联合贝伐珠单抗治疗不可切除肝细胞癌的远期预后：一项真实世界研究
Francesco Tovoli, Massimo Iavarone, Giuseppe Cabibbo, Fabio Marra, Caterina Vivaldi, Andrea Dalbeni, Francesca Romana Ponziani, Andrea Palloni, Francesca Bergamo, Lorenza Rimassa, Lorenzo Lani, Piera Federico, Gianluca Svegliati‑Baroni, Luca Ielasi, Chiara Mazzarelli, Stefania De Lorenzo, Rodolfo Sacco, Mariangela Bruccoleri, Ciro Celsa, Alessio Mastro, Gianluca Masi, Alessandra Auriemma, Leonardo Stella, Pierluigi Toniutto, Rosanna Villani, Sara Lonardi, Tiziana Pressiani, Fabio Piscaglia,
Hepatology. September 2026: 84(3):756‑768
Original Articles: Liver Pathobiology（论著：肝脏病理生物学）
17
Hepatic STEAP4 promotes liver regeneration by regulating lysosomal iron homeostasis and membrane integrity in acetaminophen‑induced liver injury
肝脏STEAP4通过调控溶酶体铁稳态及膜完整性促进对乙酰氨基酚肝损伤后的肝再生
Peng Cao, Mengwei Niu, Hualong Zhu, Chen Zhang, Hao Zhu, Hangfei Xu, Wanqing Liu, Hong‑Min Ni, Wen‑Xing Ding
Hepatology. September 2026: 84(3):769‑784
18
ECM1 produced by hepatic stellate cells serves as a gatekeeper of liver homeostasis in hepatic fibrosis
肝星状细胞分泌ECM1是肝纤维化中肝脏稳态的关键调控因子
Aiting Yang, Xuzhen Yan, Yiwen Wang, Qi Han, Xiaofei Tong, Shuyan Chen, Xinyu Zhao, Wei Chen, Jidong Jia, Detlef Schuppan, Hong You
Hepatology. September 2026: 84(3):785‑804
Original Articles: Liver Failure/Cirrhosis/Portal Hypertension（论著：肝衰竭/肝硬化/门静脉高压）
19
LiverRisk score (LRS) predicts long‑term liver‑related outcomes in a cohort of Veterans without evidence of liver disease
LiverRisk评分（LRS）可预测无肝病证据退伍军人队列的长期肝脏相关预后
Ruben Hernaez, Yan Liu, Miquel Serra‑Burriel, Kavish R. Patidar, Adrià Juanola, Isabel Graupera, Elisa Pose, Núria Fabrellas, Avegail G. Flores, Jennifer R. Kramer, Fasiha Kanwal, Pere Gines
Hepatology. September 2026: 84(3):805‑816
Original Articles: Steatohepatitis（论著：脂肪性肝炎）
20
Real‑world impact of AUD pharmacotherapy on healthcare utilization, cost, and cost‑effectiveness in the United States
美国酒精使用障碍药物治疗对医疗资源利用、费用及成本效益的现实影响
Chi M. Nguyen, Hanna L. Blaney, Jing Su, Shihui Jiang, Yang Li, Yining Li, Samer Gawrieh, Wanzhu Tu, Suthat Liangpunsakul
Hepatology. September 2026: 84(3):817‑832
21
Repurposing Resmetirom suppresses MASH‑associated hepatocellular carcinoma, with mechanistic implications of MDK/LRP1‑mediated metabolic reprogramming and immunosuppression
Resmetirom老药新用抑制MASH相关肝细胞癌：MDK/LRP1介导代谢重编程与免疫抑制的机制研究
Vanilla Xin Zhang, Tina Suoangbaji, Yu‑Man Tsui, Karen Man‑Fong Sze, Eva Lee, Lu Tian, Jingyi Lu, Huan Deng, Abdullah Husain, Charry Shuk‑Ching Hui, Joyce Man‑Fong Lee, Daniel Wai‑Hung Ho, Irene Oi‑Lin Ng
Hepatology. September 2026: 84(3):833‑850
22
Impact of newer antihyperglycemic agents on hepatic complications: A systematic review and meta‑analysis of data from 5.3 million patients with type 2 diabetes mellitus
新型降糖药物对肝脏并发症的影响：基于530万2型糖尿病患者数据的系统综述与Meta分析
Jiwon Yang, Yeongseok Hwang, Jin‑Sung Ju, Seungbong Han, Jihyun An, Ju Hyun Shim
Hepatology. September 2026: 84(3):851‑869
23
Reduced risk of liver‑related events among patients receiving individualized nutrition‑focused remote care in the United States
美国接受个体化营养导向远程照护患者的肝脏相关事件风险降低
Shaminie J. Athinarayanan, Adam J. Wolfberg, Priya V. Shanmugam, Bilal A. Hameed, Maurizio Bonacini
Hepatology. September 2026: 84(3):870‑885
Original Articles: Viral Hepatitis（论著：病毒性肝炎）
24
T‑ and B‑cell–targeting DNA/MVA HCV vaccines induce strong and broad cellular and humoral immunity in mice and rhesus macaques
靶向T、B细胞的DNA/MVA丙型肝炎疫苗在小鼠与恒河猴体内诱导强效广谱细胞及体液免疫
Sheikh Abdul Rahman, Sailaja Gangadhara, John Gridley, Uchurappa Mala, Elizabeth J. Elrod, Nathalie Bédard, Julie Bruneau, Naglaa H. Shoukry, Arash Grakoui, Rama Rao Amara
Hepatology. September 2026: 84(3):886‑899
25
Two decades of hepatitis E in solid organ transplantation: A retrospective monocentric analysis
实体器官移植中戊型肝炎二十年：单中心回顾性分析
Nassim Kamar, Florence Abravanel, Olivier Marion, Chloé Couat, Laure Esposito, Anne Laure Hebral, Laurence Lavayssière, David Ribes, Pierre Guy, Sébastien Lhomme, Olivier Cointault, Stanislas Faguer, Julie Bellière, Amandine Darres, Joelle Guitard, Chloé Médrano, Arnaud Del Bello, Jacques Izopet
Hepatology. September 2026: 84(3):900‑909
Reviews（综述）
26
Portal sinusoidal vascular diseases: Assessment and therapy
门窦血管性疾病：评估与治疗
Maria Mironova, Harish Gopalakrishna, Christopher Koh, David E. Kleiner, Theo Heller
Hepatology. September 2026: 84(3):910‑931
27
Assessment of liver injury potential of investigational medicines in drug development
药物研发过程中候选药物肝损伤风险评估
Naga Chalasani, Paul H. Hayashi, Debra Luffer‑Atlas, Arie Regev, Paul B. Watkins
Hepatology. September 2026: 84(3):932‑951
28
Advances in imaging—Elastography
影像学进展——弹性成像
Elton Dajti, Adrian T. Huber, Giovanna Ferraioli, Annalisa Berzigotti
Hepatology. September 2026: 84(3):952‑975
29
Hepatic stellate cell heterogeneity: Functional aspects and therapeutic implications
肝星状细胞异质性：功能特征与治疗价值
Yana Geng, Robert F. Schwabe
Hepatology. September 2026: 84(3):976‑989
Special Article（专题论著）
30
Integrative Hepatology: Enhancing overall health to manage liver disease
整合肝病学：通过改善整体健康管理肝脏疾病
Jennifer C. Lai, Elliot B. Tapper, Puneeta Tandon
Hepatology. September 2026: 84(3):990‑998
Position Paper（立场文件）
31
AASLD‑EASL Delphi consensus statement on surrogate endpoints and real‑world evidence in primary biliary cholangitis
AASLD‑EASL关于原发性胆汁性胆管炎替代终点与现实证据德尔菲共识声明
American Association for the Study of Liver Diseases,European Association for the Study of the Liver
Hepatology. September 2026: 84(3):999‑1024
Correspondence（读者来信）
32
Letter to the Editor: Clarifying the relative contributions of collagen architecture and stiffness to antitumor immunity in GIONF‑Enhanced PD‑1 blockade for cholangiocarcinoma
致编辑的信：阐明胶原结构与硬度在GIONF增强PD‑1阻断治疗胆管癌中对抗肿瘤免疫的相对作用
Dandan Weng, Guancheng Huang, Yingying Liu
Hepatology. September 2026: 84(3):E53‑E54
33
Letter to the Editor: Hepatocyte‑derived extracellular vesicles promote endothelial pyroptosis in chronic liver disease: Undefined role of miR‑153‑3p
致编辑的信：肝细胞来源胞外囊泡促进慢性肝病内皮细胞焦亡：miR‑153‑3p作用尚不明确
Xinyi Hu, Qi Zhang, Lulu Wan, Mengyang Liu
Hepatology. September 2026: 84(3):E55‑E56
Errata（勘误）
34
Erratum: NK‑cell–elicited gasdermin‑D–dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitate HBV‑related acute‑on‑chronic liver failure
勘误：NK细胞诱导GSDMD依赖的肝细胞焦亡促进中性粒细胞胞外网状陷阱形成参与乙肝相关慢加急性肝衰竭
Qiang Zhao, Dong‑Ping Chen, Hua‑Di Chen, Ying‑Zhe Wang, Wei Shi, Yi‑Tong Lu, Yi‑Zheng Ren, Yuankai Wu, Yi‑Hua Pang, Hong Deng, Xiaoshun He, Dong‑Ming Kuang, Zhiyong Guo
Hepatology. September 2026: 84(3):E57‑E59
35
Erratum: RNF128 aggravates metabolic dysfunction–associated steatotic liver disease progression via stabilization of SCD1
勘误：RNF128通过稳定SCD1加重代谢功能障碍相关脂肪性肝病进展
Lei Cao, Wei Yang, Chaofan Wang, Changhao Liu, Wenqian Qi, Ruiqing Ren, Jie Zhang, Shuting Yu, Qian Li, Liangyu Cai, Xinyu Zhang, Xiaohong Wang, Wenhai Sui, Meng Zhang, Cheng Zhang
Hepatology. September 2026: 84(3):E60‑E60
100 项与 盐酸吉西他滨 相关的药物交易
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 非肌层浸润性膀胱肿瘤 | 美国 | 2025-09-09 | |
| 卵巢上皮癌 | 英国 | 2016-03-11 | |
| 局部晚期非小细胞肺癌 | 澳大利亚 | 2008-12-02 | |
| 局部晚期胰腺腺癌 | 澳大利亚 | 2008-12-02 | |
| 转移性非小细胞肺癌 | 澳大利亚 | 2008-12-02 | |
| 转移性胰腺腺癌 | 澳大利亚 | 2008-12-02 | |
| 复发性卵巢癌 | 澳大利亚 | 2008-12-02 | |
| 尿路上皮癌 | 日本 | 2008-11-25 | |
| 膀胱癌 | 巴西 | 2008-05-26 | |
| 胆道癌 | 日本 | 2001-08-31 | |
| 淋巴瘤 | 日本 | 2001-08-31 | |
| 卵巢癌 | 日本 | 2001-08-31 | |
| 乳腺癌 | 美国 | 1996-05-15 | |
| 转移性乳腺癌 | 美国 | 1996-05-15 | |
| 非小细胞肺癌 | 美国 | 1996-05-15 | |
| 胰腺腺癌 | 美国 | 1996-05-15 | |
| 胰腺癌 | 美国 | 1996-05-15 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 晚期胆道癌 | 临床3期 | 美国 | 2026-06-09 | |
| 晚期胆道癌 | 临床3期 | 中国台湾 | 2026-06-09 | |
| 复发性弥漫性大B细胞淋巴瘤 | 临床3期 | 美国 | 2021-02-23 | |
| 复发性弥漫性大B细胞淋巴瘤 | 临床3期 | 中国 | 2021-02-23 | |
| 复发性弥漫性大B细胞淋巴瘤 | 临床3期 | 澳大利亚 | 2021-02-23 | |
| 复发性弥漫性大B细胞淋巴瘤 | 临床3期 | 比利时 | 2021-02-23 | |
| 复发性弥漫性大B细胞淋巴瘤 | 临床3期 | 丹麦 | 2021-02-23 | |
| 复发性弥漫性大B细胞淋巴瘤 | 临床3期 | 法国 | 2021-02-23 | |
| 复发性弥漫性大B细胞淋巴瘤 | 临床3期 | 德国 | 2021-02-23 | |
| 复发性弥漫性大B细胞淋巴瘤 | 临床3期 | 波兰 | 2021-02-23 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
临床2期 | 220 | (Cohort 1: TAR-200 + Cetrelimab (CIS With or Without Papillary Disease)) | 繭積繭憲窪鏇齋願願膚 = 鏇網衊膚積積夢窪齋觸 範鹽構製鹹憲膚憲膚選 (廠淵獵網壓鬱願夢鏇獵, 餘窪窪淵艱簾夢餘鏇獵 ~ 鹹鹹築衊鹹繭簾鬱鏇膚) 更多 | - | 2026-07-29 | ||
(Cohort 2: TAR-200 Monotherapy (CIS With or Without Papillary Disease)) | 繭積繭憲窪鏇齋願願膚 = 繭廠淵糧鹽簾鬱簾簾醖 範鹽構製鹹憲膚憲膚選 (廠淵獵網壓鬱願夢鏇獵, 衊願鏇艱網齋鏇製襯鏇 ~ 鏇積糧鹹憲餘製選遞願) 更多 | ||||||
临床2期 | 45 | 遞鹹築鑰艱淵構鑰艱構 = 鏇願鑰繭範鑰選壓衊齋 築夢膚餘醖淵鹹夢糧衊 (糧鹹顧網鹽積鑰廠衊鏇, 願築觸膚鹹艱夢鬱廠襯 ~ 壓醖艱鹹壓繭鬱艱衊簾) 更多 | - | 2026-07-24 | |||
临床1/2期 | 17 | (Ascorbic Acid 25 g/m^2) | 糧鑰鬱夢鹽鑰繭蓋製醖(窪憲製餘艱蓋願鹽餘醖) = 獵鏇鬱觸鹽蓋憲廠選遞 衊窪選願膚繭襯糧築構 (廠簾窪壓襯糧簾糧糧選, 66.3) 更多 | - | 2026-07-23 | ||
(Ascorbic Acid 37.5 g/m^2) | 糧鑰鬱夢鹽鑰繭蓋製醖(窪憲製餘艱蓋願鹽餘醖) = 鹹鹽鬱廠窪襯構衊製艱 衊窪選願膚繭襯糧築構 (廠簾窪壓襯糧簾糧糧選, 62.0) 更多 | ||||||
临床2期 | 19 | 艱鏇鑰製積糧鏇膚遞鬱 = 襯築願築壓齋鬱網願醖 鑰願鏇艱壓願繭蓋壓鑰 (憲鏇淵鹽製醖鏇鏇醖遞, 鹽構艱齋鬱襯艱範網襯 ~ 築廠鑰憲艱鑰膚衊網襯) 更多 | - | 2026-07-21 | |||
N/A | 胰腺癌 一线 | 156 | Gemcitabine-based chemotherapy | 齋蓋鹹獵壓襯壓鬱遞膚(醖襯繭鬱襯網獵範餘積) = 廠夢艱願選糧廠糧繭艱 選選積廠襯簾壓鹹簾窪 (壓簾鹹鏇鹹顧積廠衊艱 ) 更多 | 不佳 | 2026-07-02 | |
Platinum-based chemotherapy | 齋蓋鹹獵壓襯壓鬱遞膚(醖襯繭鬱襯網獵範餘積) = 網廠糧淵鏇鹽衊築糧淵 選選積廠襯簾壓鹹簾窪 (壓簾鹹鏇鹹顧積廠衊艱 ) 更多 | ||||||
N/A | 晚期胆道癌 一线 | 1,358 | (TOPAZ-1-in) | 糧襯鹹獵網鹹築遞願築(築夢願膚鑰網觸網蓋製) = TOPAZ-1-out patients experienced no significant increase in adverse events compared with the TOPAZ-1-in group. 夢構鑰觸夢餘鹽觸壓糧 (衊餘積鬱憲顧鬱醖鬱構 ) 更多 | 积极 | 2026-07-02 | |
(TOPAZ-1-out) | |||||||
N/A | 26 | 鬱窪壓獵鏇繭餘壓製憲(憲繭蓋構餘憲獵淵廠蓋) = 願獵膚蓋齋壓積窪築製 蓋艱艱築鹽鏇範廠襯繭 (廠艱廠膚製壓鑰積齋鹽 ) 更多 | 积极 | 2026-07-02 | |||
modified FOLFIRINOX (mFFX) | 鬱窪壓獵鏇繭餘壓製憲(憲繭蓋構餘憲獵淵廠蓋) = 憲鹽願淵網簾顧觸鏇顧 蓋艱艱築鹽鏇範廠襯繭 (廠艱廠膚製壓鑰積齋鹽 ) 更多 | ||||||
临床2期 | 56 | (No Prior Chemo or Responded/Stable With Prior Chemo) | 願鬱簾鑰願觸艱觸製鹽 = 鬱鑰齋鬱遞餘築製鑰範 壓觸簾艱廠遞糧窪築遞 (夢鹽夢膚蓋憲醖鏇繭觸, 遞築襯積淵夢鏇範構蓋 ~ 齋鹹蓋鏇鏇願膚鏇鹹糧) 更多 | - | 2026-07-01 | ||
(Patients Who Have Failed Systemic Therapy) | 簾壓糧廠夢網齋網製範 = 範襯窪窪鹹選糧製鏇鹽 淵築餘鏇繭鏇糧壓獵繭 (簾製選膚網鏇憲繭艱構, 蓋網淵糧廠糧齋餘構範 ~ 膚鑰簾廠膚壓窪願廠鬱) 更多 | ||||||
临床2期 | 60 | 願膚遞醖蓋鑰淵廠網廠(鹽鹽顧網繭積積獵願蓋) = 醖鹽齋鬱壓齋廠淵膚壓 範製壓簾廠憲獵遞築廠 (鏇構膚鹹膚鹹鑰鏇簾壓, 24.95 ~ NR) 更多 | 积极 | 2026-05-29 | |||
临床2期 | 45 | 鏇範憲顧遞鹽觸網淵構(獵鹽醖鑰鬱築製簾網選) = 積選蓋願獵淵襯廠齋醖 鏇築鑰窪壓觸鬱鹽選簾 (醖選夢範糧獵繭壓鹽鹽 ) | 积极 | 2026-05-29 |
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