Abstract 2611: Function blocking ERBB3 antibody inhibits adaptive response to RAF inhibitor

Abstract

Abstract ERBB3/HER3 is a member of the EGFR family of receptor tyrosine kinase. Our lab recently showed that treating melanoma cells with the FDAapproved small molecule BRAF inhibitor vemurafenib leads to an increase in ERBB3 signaling when grown in the presence of its ligand neuregulin (NRG1). Here, we show that targeting ERBB3 with a monoclonal antibody inhibits its activation and downstream signaling in the presence of vemurafenib and NRG1. This inhibition of ERBB3 led to a decrease in proliferation and increase in apoptosis in vitro as measured by EdU and AnnexinV/PI staining. Targeting ERBB3 in combination with mutant BRAF in vivo resulted in a delay of tumor re-growth in immune deficient mice compared to targeting mutant BRAF alone. Taken together, these results indicate that targeting ERBB3 in combination with mutant BRAF in melanoma may help enhance the initial effects of vemurafenib in the clinic. Citation Format: Curtis Harrison Kugel, Edward J. Hartsough, Michael A. Davies, Andrew E. Aplin. Function blocking ERBB3 antibody inhibits adaptive response to RAF inhibitor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2611. doi:10.1158/1538-7445.AM2014-2611