HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates
Alberto Ocaña, Eitan Amir, Atanasio Pandiella, Alberto Ocaña, Eitan Amir, Atanasio Pandiella
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.
Conflict of interest statement
The authors declare that they have no competing interests.
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Source: PubMed