1. Core melanoma escape pathways during disease progression on BRAF inhibitor therapy.
Core melanoma escape pathways during disease progression on BRAF inhibitor therapy. A, representative photographs (patient #25) of initial vemurafenib response (incomplete response with residual tumor volume) and later acquired BRAFi resistance, which occurred at a site of incompletely shrunken tumor. B, the relative distribution of MAPK-reactivating mechanisms among disease-progressive melanomas where such mechanisms were detected. C, the relative distribution of core pathways (MAPK vs. PI3K–PTEN–AKT) and hitherto unknown mechanisms among all melanomas featuring disease progression. D, nonsynonymous mutations in the PI3K–PTEN–AKT core drug escape pathway detected only in disease-progression tumors. The schematics show the locations of mutations in the protein domain structures and their corresponding source patients and tissues. E, signaling schematics of PI3K–PTEN–AKT pathway components mutated in biopsies of growing melanomas with acquired BRAF inhibitor resistance (PIK3CA, p110α; PIK3R2, p85β). F, focal copy number loss of PTEN in disease-progression melanoma of patient #11.
Hubing Shi et al. Cancer Discovery 2014;4:80-93
©2014 by American Association for Cancer Research