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Review
. 2020 Jan 31;22(1):15.
doi: 10.1186/s13058-020-1252-7.

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

Alberto Ocaña  1   2   3 , Eitan Amir  4 , Atanasio Pandiella  5   6
Affiliations
Review

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

Alberto Ocaña et al. Breast Cancer Res. .

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.

Keywords: ADCs; DS-8201; HER2 heterogeneity; HER2 resistance; T-DM1.

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Conflict of interest statement

The authors declare that they have no competing interests.

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