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Review
. 2017 Mar 28;8(13):22203-22217.
doi: 10.18632/oncotarget.14729.

Dysregulations in the PI3K pathway and targeted therapies for head and neck squamous cell carcinoma

Yi Cai  1 , Sonam Dodhia  1 , Gloria H Su  1   2   3
Affiliations
Review

Dysregulations in the PI3K pathway and targeted therapies for head and neck squamous cell carcinoma

Yi Cai et al. Oncotarget. .

Abstract

The phosphoinositide 3-kinase (PI3K) signaling pathway is the most commonly mutated pathway in head and neck squamous cell carcinoma (HNSCC). There are several drugs targeting members of the PI3K signaling pathway in development for HNSCC. In this article, we review the genetic alterations reported in the pathway pertinent to HNSCC, various agents in development targeting various mediators of the pathway, results from clinical trials, and remaining challenges in the development of PI3K pathway inhibitors.

Keywords: PI3K inhibitor; PI3K signaling; PIK3CA mutation; head and neck squamous cell carcinoma; personalized medicine.

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Conflict of interest statement

CONFLICTS OF INTEREST

There is no conflict of interest.

Figures

Figure 1
Figure 1. PIK3CA point mutation rates in TCGA cohorts
Analysis of TCGA cohorts of HNSCC, breast cancer, and colorectal cancer was performed to determine rates of point mutations in PIK3CA. The top 30 most frequent mutations when analyzing all TCGA tumor samples were selected. The residues affected by these mutations are depicted along with the corresponding rates of mutation. The mutation rates represent the percentage of total PIK3CA mutations affecting each residue for the various types of tumor. Abbreviations: ABD, adaptor-binding domain; RBD, RAS-binding domain; C2, protein-kinase-C homology-2 domain.
Figure 2
Figure 2. The PI3K signaling pathway's key players and inhibitors under investigation in HNSCC trials
See this image and copyright information in PMC

References

    1. Iglesias-Bartolome R, Martin D Gutkind JS. Exploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets. Cancer Discov. 2013;7:722–725. - PMC - PubMed
    1. Lui VW, Hedberg ML, Li H, Vangara BS, Pendleton K, Zeng Y, Lu Y, Zhang Q, Du Y, Gilbert BR, Freilino M, Sauerwein S, Peyser ND, et al. Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov. 2013;7:761–769. - PMC - PubMed
    1. Engelman JA, Luo J Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;8:606–619. - PubMed
    1. Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;5573:1655–1657. - PubMed
    1. Burris HA., 3rd Overcoming acquired resistance to anticancer therapy: focus on the PI3K/AKT/mTOR pathway. Cancer Chemother Pharmacol. 2013;4:829–842. - PubMed

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