Functional characterization of a novel somatic oncogenic mutation of PIK3CB

A tumor-driving mutation found in men with malignancies including advanced prostate cancer could be targeted with a directed drug inhibitor. Andrew Whale, Stephen Shuttleworth and colleagues from Karus Therapeutics in Oxfordshire, UK, characterized a mutation originally found in two patients in a previously published genomic study of 150 men with metastatic prostate cancer. This mutation fell in a gene called PIK3CB, which encodes the p110β catalytic subunit of phosphoinositide 3-kinase (PI3K), a class of important signaling enzymes that govern cellular metabolism, growth and survival. The researchers showed that the mutation promotes the proliferation and migration of cancer cells, and that a p110β inhibitor limited PI3K signaling in cancer cells, restricting their growth. The findings build the case for personalized drug therapies involving PI3K inhibitors that target precise mutations found in individual patient tumors.