Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation

摘要: EGF receptor (EGFR) inhibition is efficacious in cancer therapy, but initially sensitive tumors often develop resistance. In this study, we investigated the potential to overcome acquired resistance EGFR inhibitors with MEHD7945A, a monoclonal antibody that dually targets and HER3 (ErbB3). cells resistant cetuximab erlotinib, found not single target inhibitors, could inhibit tumor growth cell-cycle progression parallel EGFR/HER3 signaling pathway modulation. MEHD7945A was more effective than combination of anti-HER3 at inhibiting both growth. human xenograft models, confirmed greater antitumor potency or erlotinib. retained potent activity refractory inhibitor alone. Furthermore, also limited cross-resistance radiation inhibitor-resistant by modulating repair processes control apoptotic cell death. Taken together, our findings confirm an important role compensatory development offer preclinical proof-of-concept can effectively