HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.
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.
['Ocaña|Alberto|A|', 'Amir|Eitan|E|', 'Pandiella|Atanasio|A|']
D001943:Breast Neoplasms D060965:Clonal Evolution D019008:Drug Resistance, Neoplasm D005260:Female D006801:Humans D018796:Immunoconjugates D018719:Receptor, ErbB-2
HER2 heterogeneity T-DM1 ADCs DS-8201 HER2 resistance