HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.

ABSTRACT: BACKGROUND:There has been substantial interest in HER2 intratumoral heterogeneity as an explanation for the development of resistance to anti-HER2 therapies in breast cancer, particularly to trastuzumab emtansine (T-DM1). METHODS:Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer. RESULTS:We describe results from clinical studies reporting the effect of anti-HER2 strategies particularly ADCs and their mechanistic effect. We review biological findings underlying HER2 heterogeneity and its implication in the development of novel anti-HER2 drugs including new ADCs in clinical development like trastuzumab deruxtecan (DS-8201). CONCLUSIONS:We suggest potential mechanisms to optimize these compounds and thei

SUBMITTER: Ocana A 

PROVIDER: S-EPMC6995165 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature