title: The determinants of head and neck cancer: Unmasking the PI3K pathway mutations.
abstract: Studies attempting to identify and understand the function of mutated genes and deregulated molecular pathways in cancer have been ongoing for many years. The PI3K-PTEN-mTOR signaling pathway is one of the most frequently deregulated pathways in cancer.PIK3CAmutations are found 11%-33% of head and neck cancer (HNC). The hotspot mutation sites forPIK3CAare E542K, E545K and H1047R/L. The PTEN somatic mutations are in 9-23% of HNC, and they frequently cluster in the phosphatase domain of PTEN protein.PTENloss of heterozygosity (LOH) ranges from 41%-71% and loss of PTEN protein expression occurs in 31.2% of the HNC samples. PIK3CA and PTEN are key molecules in the PI3K-PTEN-mTOR signaling pathway. In this review, we provided a comprehensive overview of mutations in the PI3K-PTEN-mTOR molecular circuitry in HNC, including PI3K family members, TSC1/TSC2, PTEN, AKT, and mTORC1 and mTORC2 complexes. We discussed how these genetic alterations may affect protein structure and function. We also highlight the latest discoveries in protein kinase and tumor suppressor families, emphasizing how mutations in these families interfere with PI3K signaling. A better understanding of the mechanisms underlying cancer formation, progression and resistance to therapy will inform selection of novel genomic-based personalized therapies for head and neck cancer patients.
authors.affiliation: Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, 48109-1078, USA ; International Research Center, A. C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Giudice
authors.affiliation: Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, 48109-1078, USA.
authors.forename: Cristiane H
authors.initials: CH
authors.lastname: Squarize
keywords: HNSCC; mutations; oncogenomics; review; tumor sequencing