PI3 '-Kinase Inhibition Forestalls the Onset of MEK1/2 Inhibitor Resistance in BRAF-Mutated Melanoma
Marian M Deuker, Victoria Marsh Durban, Wayne A Phillips, Martin McMahon
Cancer Discovery | AMER ASSOC CANCER RESEARCH | Published : 2015
UNLABELLED: Phosphatidylinositide 3' (PI3')-lipid signaling cooperates with oncogenic BRAF(V600E) to promote melanomagenesis. Sustained PI3'-lipid production commonly occurs via silencing of the PI3'-lipid phosphatase PTEN or, less commonly, through mutational activation of PIK3CA, encoding the 110-kDa catalytic subunit of PI3'-kinase-α (PI3Kα). To define the PI3K catalytic isoform dependency of BRAF-mutated melanoma, we used pharmacologic, isoform-selective PI3K inhibitors in conjunction with melanoma-derived cell lines and genetically engineered mouse (GEM) models. Although BRAF(V600E)/PIK3CA(H1047R) melanomas were sensitive to the antiproliferative effects of selective PI3Kα blockade, inh..View full abstract
Awarded by National Cancer Institute
Awarded by NATIONAL CANCER INSTITUTE
Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
This research was supported by grants from the National Health and Medical Research Council of Australia (to W.A. Phillips) and the National Cancer Institute (CA176839; to M. McMahon), the Melanoma Research Alliance (to M. McMahon), and the National Comprehensive Cancer Network (to M. McMahon).