Abstract

Antibody-drug conjugates (ADCs) are a rapidly developing therapeutic approach in cancer treatment that has shown remarkable activity in breast cancer. Currently, there are two ADCs approved for the treatment of human epidermal growth factor receptor 2-positive breast cancer, one for triple-negative breast cancer, and multiple investigational ADCs in clinical trials. However, drug resistance has been noticed in clinical use, especially in trastuzumab emtansine. Here, the mechanisms of ADC resistance are summarized into four categories: antibody-mediated resistance, impaired drug trafficking, disrupted lysosomal function, and payload-related resistance. To overcome or prevent resistance to ADCs, innovative development strategies and combination therapy options are being investigated. Analyzing predictive biomarkers for optimal therapy selection may also help to prevent drug resistance.

Details

Title
Resistance to antibody-drug conjugates in breast cancer: mechanisms and solutions
Author
Yu-Fei, Chen 1 ; Ying-ying, Xu 2 ; Zhi-Ming Shao 1 ; Ke-Da Yu 1   VIAFID ORCID Logo 

1  Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, P. R. China; Shanghai Medical College, Fudan University, Shanghai, P. R. China 
2  Department of Breast Surgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, P. R. China 
Pages
297-337
Section
REVIEW
Publication year
2023
Publication date
Mar 2023
Publisher
John Wiley & Sons, Inc.
e-ISSN
2523-3548
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1002/cac2.12387
ProQuest document ID
2786026712
Copyright
© 2023. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.