Alterations and molecular targeting of the GSK-3 regulator, PI3K, in head and neck cancer

Biochim Biophys Acta Mol Cell Res. 2020 Jun;1867(6):118679. doi: 10.1016/j.bbamcr.2020.118679. Epub 2020 Feb 19.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a highly morbid, genetically unstable disease derived from the mucoepithelium of the upper aerodigestive tract. Recent characterization of this disease has implicated the PI3K-Akt-mTOR pathway as one of the most frequently dysregulated pathways. As such, there are several classes of PI3K inhibitors currently undergoing clinical trials. In this article, we review the PI3K pathway, mutations of this pathway in HNSCC, drugs that target PI3K, the impact of these agents on the PI3K and GSK-3 signaling axes, ongoing clinical trials evaluating PI3K inhibitors, and the challenges of using these drugs in the clinic. This article is part of a Special Issue entitled: GSK-3 and related kinases in cancer, neurological and other disorders edited by James McCubrey, Agnieszka Gizak and Dariusz Rakus.

Keywords: GSK-3; HNSCC; Head and neck squamous cell carcinoma; PI3K; PIK3CA.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism*
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism*

Substances

  • Protein Kinase Inhibitors
  • Glycogen Synthase Kinase 3