The PI3K/AKT Pathway and Renal Cell Carcinoma

Huifang Guo, Peter German, Shanshan Bai, Sean Barnes, Wei Guo, Xiangjie Qi, Hongxiang Lou, Jiyong Liang, Eric Jonasch, Gordon B. Mills, Zhiyong Ding

    Research output: Contribution to journalReview article

    109 Scopus citations

    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, PI3K 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.

    Original languageEnglish (US)
    Pages (from-to)343-353
    Number of pages11
    JournalJournal of Genetics and Genomics
    Volume42
    Issue number7
    DOIs
    StatePublished - Jul 20 2015

    Keywords

    • AKT
    • MTOR
    • PI3K
    • Renal cell carcinoma
    • Targeted therapy

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics

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  • Cite this

    Guo, H., German, P., Bai, S., Barnes, S., Guo, W., Qi, X., Lou, H., Liang, J., Jonasch, E., Mills, G. B., & Ding, Z. (2015). The PI3K/AKT Pathway and Renal Cell Carcinoma. Journal of Genetics and Genomics, 42(7), 343-353. https://doi.org/10.1016/j.jgg.2015.03.003