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

<bold>Background: </bold>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).<bold>Methods: </bold>Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.<bold>Results: </bold>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).<bold>Conclusions: </bold>We suggest potential mechanisms to optimize these compounds and their future clinical implementation. [ABSTRACT FROM AUTHOR]