摘要
Class I phosphoinositide 3-kinase(PI3K)enzymes have attracted considerable attention as drug targets in cancer therapy over the last 20 years.The signaling pathway triggered by class I PI3Ks is dysregulated in a range of tumor types,impacting cell proliferation,survival and apoptosis.Frequent oncogenic mutations of PIK3CA have previously been discovered.In contrast,reports of PIK3CB mutations have been limited;however,in most cases,those that have been identified have been shown to be activating and oncogenic.The functional characterization of a PIK3CB catalytic domain mutant,p110β^(E1051K),first discovered by others in castrateresistant prostate cancer(mCRPC),is outlined in this report;our data suggest that p110β^(E1051K)is a gain-of-function mutation,driving PI3K signaling,tumorigenic cell growth and migration.Tumor cells expressing p110β^(E1051K)are sensitive to p110βinhibition;its characterization as an oncogenic driver adds to the rationale for targeting p110βand indicates a continuing need to further develop specific PI3K inhibitors for clinical development in cancer therapy.
