Resistance to antibody-drug conjugates:A review  

作　　者：Sijia Li Xinyu Zhao Kai Fu Shuangli Zhu Can Pan Chuan Yang Fang Wang Kenneth K.W.To Liwu Fu 

机构地区：[1]State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangdong Esophageal Cancer Institute,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou 510060,China [2]School of Pharmacy,the Chinese University of Hong Kong,Hong Kong 999077,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第2期737-756,共20页药学学报(英文版)

基　　金：supported by the National Natural Science Foundation of China(Nos.U21A20421 and 82073882);the Key Project of Science Technology Program of Guangzhou(No.2023B03J0029);Guangdong Basic and Applied Basic Research Foundation(No.2023B1515130009);Key-Area Research and Development Program of Guangdong Province(2023B1111020005).

摘　　要：Antibody-drug conjugates(ADCs)are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker.Currently,15 ADCs have been clinically approved worldwide.More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs.ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development.It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells,thereby producing promising antitumor efficacy and favorable adverse effect profiles.However,emergence of drug resistance has severely hindered the clinical efficacy of ADCs.In this review,we introduce the structure and mechanism of ADCs,describe the development of ADCs,summarized the latest research about the mechanisms of ADC resistance,discussed the strategies to overcome ADCs resistance,and predicted biomarkers for treatment response to ADC,aiming to contribute to the development of ADCs in the future.

关 键 词：Antibodyedrug conjugates Drug resistance Combination therapy Targeted therapy Cytotoxic therapy CANCER ONCOTHERAPY Predictive biomarker 

分 类 号：R730.5[医药卫生—肿瘤]