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The PI3K/AKT Pathway and Renal Cell Carcinoma
Abstract:The phosphatidylinositol 3 kinase(PI3K)/AKT pathway is genetically targeted in more pathway components and in more tumor types than any other growth factor signaling pathway,and thus is frequently activated as a cancer driver.More importantly,the PI3K/AKT pathway is composed of multiple bifurcating and converging kinase cascades,providing many potential targets for cancer therapy.Renal cell carcinoma(RCC) is a high-risk and high-mortality cancer that is notoriously resistant to traditional chemotherapies or radiotherapies.The PI3K/AKT pathway is modestly mutated but highly activated in RCC,representing a promising drug target.Indeed,PI3 K pathway inhibitors of the rapalog family are approved for use in RCC.Recent large-scale integrated analyses of a large number of patients have provided a molecular basis for RCC,reiterating the critical role of the PI3K/AKT pathway in this cancer.In this review,we summarize the genetic alterations of the PI3K/AKT pathway in RCC as indicated in the latest large-scale genome sequencing data,as well as treatments for RCC that target the aberrant activated PI3K/AKT pathway.
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