HER3 targeting with an antibody-drug conjugate bypasses resistance to anti-HER2 therapies.

ABSTRACT: Despite impressive clinical benefit obtained with anti-HER2-targeted therapies, in advances stages, especially in the metastatic setting, HER2-positive tumors remain incurable. Therefore, it is important to develop novel strategies to fight these tumors, especially when they become resistant to available therapies. We show here that the anti-HER3 antibody-drug conjugate EV20/MMAF exerted potent anti-tumoral properties against several models of primary resistance and secondary resistance to common anti-HER2 available therapies, including trastuzumab, lapatinib, neratinib, and trastuzumab-emtansine. HER3 was expressed in these HER2⁺ breast cancer cells and knockdown experiments demonstrated that HER3 expression was required for the action of EV20/MMAF. In mice injected with trastu

SUBMITTER: Gandullo-Sanchez L 

PROVIDER: S-EPMC7207167 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature