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REVIEW article

Front. Pharmacol.

Sec. Pharmacology of Anti-Cancer Drugs

Navigating Hepatotoxicity of Antibody-Drug Conjugates: From Mechanistic Insights to Clinical and Postmarketing Evidence

Provisionally accepted
Yinuo DongYinuo Dong1Yang ZhiYang Zhi1Xiaoyun LiXiaoyun Li1,2Mingyang MaMingyang Ma3Minyan YeMinyan Ye4Sha HuangSha Huang4Jieting TangJieting Tang1Wei ZhongWei Zhong1Xiaohong LeiXiaohong Lei1Yimin MaoYimin Mao1,5*
  • 1Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
  • 2The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
  • 3Tianjin Medical University General Hospital Department of General Surgery, Tianjin, China
  • 4Fujian Provincial Cancer Hospital, Fuzhou, China
  • 5Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

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Antibody-drug conjugates (ADCs) are rapidly developing targeted cancer therapeutic agents that combine specific monoclonal antibodies with cytotoxic agents. Currently, 17 ADCs are approved for the global market for treating hematological and solid tumors with more than 100 ADCs are in phase III clinical trials. ADC-induced hepatotoxicity is a significant concern with unclear mechanisms, and the incidence of hepatic adverse events (AEs) varies across different ADCs. Most hepatic AEs are moderate; however, some ADCs can cause life threatening or fatal AEs. The management of hepatic AEs is limited and is mainly based on product labeling information and the recommendations of study investigators. Therefore, it is critical to raise awareness among oncologists regarding ADC-related hepatotoxicity, and collaboration between oncologists and hepatologists is recommended to provide effective support. This review is the first to focus the hepatotoxicity of ADC, provide an overview of approved ADCs, summarize the potential mechanisms underlying hepatotoxicity, discuss the hepatic toxicities reported in clinical trials and postmarketing studies, and integrate the current recommended management strategies. This article will serve as a valuable resource for medical practitioners in comprehending and managing ADC-related hepatotoxicity, while facilitating further considerations regarding the clinical application of these novel agents.

Keywords: Antibody-drug conjugate, Clinical Trial, Adverse event, Hepatotoxicity, Immunotherapy

Received: 28 Aug 2025; Accepted: 11 Nov 2025.

Copyright: © 2025 Dong, Zhi, Li, Ma, Ye, Huang, Tang, Zhong, Lei and Mao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yimin Mao, maoym11968@163.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material