The PI3K/AKT Pathway and Renal Cell Carcinoma

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 bifurcat...

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Published inJournal of genetics and genomics Vol. 42; no. 7; pp. 343 - 353
Main Authors Guo, Huifang, German, Peter, Bai, Shanshan, Barnes, Sean, Guo, Wei, Qi, Xiangjie, Lou, Hongxiang, Liang, Jiyong, Jonasch, Eric, Mills, Gordon B., Ding, Zhiyong
Format Journal Article
LanguageEnglish
Published China Elsevier Ltd 20.07.2015
Subjects
AKT
Animals
Antineoplastic Agents - therapeutic use
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - metabolism
drugs
Humans
Models, Biological
mTOR
neoplasm cells
neoplasms
patients
phosphatidylinositol 3-kinase
Phosphatidylinositol 3-Kinase - metabolism
PI3K
Proto-Oncogene Proteins c-akt - metabolism
RCC
Renal cell carcinoma
sequence analysis
signal transduction
Signal Transduction - drug effects
Targeted therapy
therapeutics
信号通路
基因组测序
生长因子
癌症治疗
碾压混凝土
磷脂酰肌醇3激酶
肾细胞
mTOR
AKT
PI3K
Renal cell carcinoma
Targeted therapy
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Summary: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.
Bibliography:PI3K; AKT; mTOR; Renal cell carcinoma; Targeted therapy
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.
11-5450/R
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ISSN:1673-8527
DOI:10.1016/j.jgg.2015.03.003