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.
J Genet Genomics. 2015 Jul 20;42(7):343-53. doi: 10.1016/j.jgg.2015.03.003. Epub 2015 Mar 19.
Guo H1, German P2, Bai S2, Barnes S1, Guo W1, Qi X3, Lou H4, Liang J1, Jonasch E2, Mills GB5, Ding Z6.
1 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
2 Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
3 Department of Radiation Oncology, People's Hospital of Linzi District, Zibo 255400, China.
4 Department of Natural Products Chemistry, Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
5 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
6 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.