Abstract PR06: A co-clinical assessment of patterns of BRAF inhibitor resistance

The acquired resistance of melanomas to BRAF inhibitors is now well-described, indicating many mechanisms including point mutations, amplifications, and alternative splicing. Here, we present a combined assessment of patient samples at both the RNA and protein levels. In parallel, we conducted a co-clinical mouse trial using a novel BRAF-driven model. We demonstrate that the response and resistance of the mouse melanomas closely parallels that of the human patient samples on both phenotypic and molecular levels, demonstrating multiple mechanisms of resistance that mirror the patient findings. On the basis of the combined data, we suggest that BRAF inhibitor-resistant melanomas can readily be categorized using economical and rapid protein array technology. This suggests that analyzing protein patterns offers a means of categorizing tumor resistance mechanisms even in the absence of identified driving genetic or epigenetic lesion(s). In summary, our results demonstrate the utility of a co-clinical assessment system and offer a cost-efficient means of categorizing patterns of BRAF inhibitor resistance in human patient samples within a clinically-meaningful timeframe.

Citation Format: Lawrence N. Kwong, Genevieve Boland, Dennie T. Frederick, Timothy Helms, John P. Miller, Shan Jiang, Zachary A. Cooper, Alexei Protopopov, Gordon B. Mills, Keith Flaherty, Jennifer A. Wargo, Lynda Chin. A co-clinical assessment of patterns of BRAF inhibitor resistance. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr PR06.