학술논문

Mechanisms of Resistance to Antibody-Drug Conjugates.
Document Type
Article
Source
International Journal of Molecular Sciences. Jun2023, Vol. 24 Issue 11, p9674. 21p.
Subject
*ANTIBODY-drug conjugates
*MONOCLONAL antibodies
*BISPECIFIC antibodies
*BLOOD diseases
*IMMUNE checkpoint inhibitors
*METASTATIC breast cancer
*PROTEIN-tyrosine kinase inhibitors
*PROGRAMMED cell death 1 receptors
Language
ISSN
1661-6596
Abstract
The treatment of cancer patients has dramatically changed over the past decades with the advent of monoclonal antibodies, immune-checkpoint inhibitors, bispecific antibodies, and innovative T-cell therapy. Antibody-drug conjugates (ADCs) have also revolutionized the treatment of cancer. Several ADCs have already been approved in hematology and clinical oncology, such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG) for the treatment of metastatic breast cancer, and enfortumab vedotin (EV) for the treatment of urothelial carcinoma. The efficacy of ADCs is limited by the emergence of resistance due to different mechanisms, such as antigen-related resistance, failure of internalization, impaired lysosomal function, and other mechanisms. In this review, we summarize the clinical data that contributed to the approval of T-DM1, T-DXd, SG, and EV. We also discuss the different mechanisms of resistance to ADCs, as well as the ways to overcome this resistance, such as bispecific ADCs and the combination of ADCs with immune-checkpoint inhibitors or tyrosine-kinase inhibitors. [ABSTRACT FROM AUTHOR]