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

doi:10.1016/j.jgg.2015.03.003

Volume 42 Issue 7

Jul. 2015

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Article Navigation > Journal of Genetics and Genomics > 2015 > 42(7): 343-353

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The PI3K/AKT Pathway and Renal Cell Carcinoma

doi: 10.1016/j.jgg.2015.03.003

a
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
b
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
c
Department of Radiation Oncology, People's Hospital of Linzi District, Zibo 255400, China
d
Department of Natural Products Chemistry, Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China

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Corresponding author: E-mail address: gmills@mdanderson.org (Gordon B. Mills); E-mail address: zding@mdanderson.org (Zhiyong Ding)
Received Date: 2014-12-18
Accepted Date: 2015-03-11
Rev Recd Date: 2015-03-03

Available Online: 2015-03-19

Publish Date: 2015-07-20

Abstract

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.
- PI3K,
- AKT,
- mTOR,
- Renal cell carcinoma,
- Targeted therapy

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References(93)

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