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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 their future clinical implementation.

SUBMITTER: Ocana A

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

REPOSITORIES: biostudies-literature

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

Ocaña Alberto A Amir Eitan E Pandiella Atanasio A

Breast cancer research : BCR 20200131 1

<h4>Background</h4>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).<h4>Methods</h4>Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.<h4>Results</h4>We describe results from clinical studies reporting the effect of anti-HER2 strategies particularly ...[more]

PMID: 32005279

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