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Review
. 2015 Jul 20;42(7):343-53.
doi: 10.1016/j.jgg.2015.03.003. Epub 2015 Mar 19.

The PI3K/AKT Pathway and Renal Cell Carcinoma

Huifang Guo  1 , Peter German  2 , Shanshan Bai  2 , Sean Barnes  1 , Wei Guo  1 , Xiangjie Qi  3 , Hongxiang Lou  4 , Jiyong Liang  1 , Eric Jonasch  2 , Gordon B Mills  5 , Zhiyong Ding  6
Affiliations
Review

The PI3K/AKT Pathway and Renal Cell Carcinoma

Huifang Guo et al. J Genet Genomics. .

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.

Keywords: AKT; PI3K; Renal cell carcinoma; Targeted therapy; mTOR.

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Figures

Fig. 1
Fig. 1
Schematic diagram of the PI3K/AKT pathway.
Fig. 2
Fig. 2
Genetic alteration frequency of 20 representative components of the PI3K/AKT pathway across 25 cancer types in The Cancer Genome Atlas (TCGA) database at cBioPortal. We surveyed the mutation and copy number alteration rates of the panel components in the latest provisional TCGA datasets at cBioPortal, including uterine corpus endometrial carcinoma (Uterine), glioblastoma multiforme (GBM), lung squamous cell carcinoma (Lung squ), uterine carcinosarcoma (Uterine CS), ovarian serous cystadenocarcinoma (Ovarian), bladder urothelial carcinoma (Bladder), breast invasive carcinoma (Breast), stomach adenocarcinoma (Stomach), head and neck squamous cell carcinoma (Head & neck), cervical squamous cell carcinoma and endocervical adenocarcinoma (Cervical), skin cutaneous melanoma (Melanoma), lung adenocarcinoma (Lung adeno), prostate adenocarcinoma (Prostate), adrenocortical carcinoma (ACC), colorectal adenocarcinoma (Colorectal), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), sarcoma (Sarcoma), pancreatic adenocarcinoma (Pancreas), brain lower grade glioma (Glioma), kidney chromophobe (chRCC), liver hepatocellular carcinoma (Liver), kidney renal papillary cell carcinoma (pRCC), kidney renal clear cell carcinoma (ccRCC), acute myeloid leukemia (AML), and thyroid carcinoma (Thyroid).
Fig. 3
Fig. 3
Genetic alterations of 20 representative components of the PI3K/AKT pathway in clear cell renal cell carcinoma. We surveyed the mutations and copy number alterations of the PI3K/AKT panel components in the latest provisional TCGA dataset of ccRCC at cBioPortal. Small grey rectangles represent patients. Genes and alteration rates are indicated to the left.
See this image and copyright information in PMC

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