Journal article
Multiple gastrointestinal polyps in patients treated with BRAF inhibitors
RK Amaravadi, KE Hamilton, X Ma, S Piao, A Del Portillo, KL Nathanson, MS Carlino, GV Long, I Puzanov, X Xu, JJD Morrissette, KY Tsai, KT Flaherty, JA Sosman, GR Goodman, GA McArthur, AK Rustgi, DC Metz, LM Schuchter, PB Chapman Show all
Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2015
Abstract
Purpose: BRAF inhibitors (BRAFi) extend survival in BRAFmutant melanoma but can promote the growth of Ras-mutant neoplasms. This study determined if gastrointestinal polyps found in BRAFi-treated patients harbored Ras mutations. Experimental Design: Colonic and gastric polyps were identified and resected from BRAFi-treated melanoma patients. Nextgeneration sequencing (NGS) was performed on polyps. The ability of BRAFi to promote polyp formation was functionally characterized in Apc Min+/- mice. MAPK and b-catenin pathway activity was assessed by immunohistochemistry in mouse and human polyps. Results: Fourteen patients treated with BRAFi underwent endoscopy to assess for polyps. Seven out of..
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Awarded by National Cancer Institute
Funding Acknowledgements
Funding for this work was provided in part by Genentech through a sponsored research agreement with University of Pennsylvania (to R.K. Amaravadi). Additional resources used included the Molecular Pathology and Imaging, Molecular Biology and Gene Expression, and Transgenic and Chimeric Mouse Cores of the University of Pennsylvania Molecular Studies in Digestive and Liver Diseases Center (NIH/NIDDK P30 DK050306). DNA sequencing was performed using the Abramson Cancer Center Genomics Core services (P30 CA016520).