Deregulation of the phosphatidylinositide 3-kinase(PI3K) and mammalian target of rapamycin(mTOR) signaling pathway occurs frequently in a wide range of human cancers and is a major driving force in tumorigenesis.Thus,...Deregulation of the phosphatidylinositide 3-kinase(PI3K) and mammalian target of rapamycin(mTOR) signaling pathway occurs frequently in a wide range of human cancers and is a major driving force in tumorigenesis.Thus,small molecules targeting this pathway are under active development as anticancer therapeutics.Although small-molecule inhibitors of the PI3K-mTOR pathway have shown promising clinical efficacy against human cancers,the emergence of drug resistance may limit their success in the clinic.To date,several resistance mechanisms,including both PI3K-dependent and-independent mechanisms,have been described.Here,we summarize the current understanding of resistance mechanisms to PI3K-mTOR inhibitors and discuss potential strategies for overcoming resistance for potential clinical application.展开更多
文摘Deregulation of the phosphatidylinositide 3-kinase(PI3K) and mammalian target of rapamycin(mTOR) signaling pathway occurs frequently in a wide range of human cancers and is a major driving force in tumorigenesis.Thus,small molecules targeting this pathway are under active development as anticancer therapeutics.Although small-molecule inhibitors of the PI3K-mTOR pathway have shown promising clinical efficacy against human cancers,the emergence of drug resistance may limit their success in the clinic.To date,several resistance mechanisms,including both PI3K-dependent and-independent mechanisms,have been described.Here,we summarize the current understanding of resistance mechanisms to PI3K-mTOR inhibitors and discuss potential strategies for overcoming resistance for potential clinical application.