The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, cross-talk, and therapies

Oral Dis. 2015 Oct;21(7):815-25. doi: 10.1111/odi.12206. Epub 2013 Dec 23.


Head and neck squamous cell carcinoma (HNSCC) is one of the most morbid, mortal, and genetically diverse malignancies. Although HNSCC is heterogeneous in nature, alterations in major components of the PI3K/Akt/mTOR pathway are consistently observed throughout the majority of HNSCC cases. These alterations include genetic aberrations, such as mutations or DNA copy number variations, and dysregulation of mRNA or protein expression. In normal physiology, the PI3K/Akt/mTOR axis regulates cell survival, growth, and metabolism. However, alterations in this pathway lead to the malignant phenotype which characterizes HNSCC, among many other cancers. For this reason, both pharmaceutical companies and academic institutions are actively developing and investigating inhibitors of PI3K, Akt, and mTOR in preclinical and clinical studies of HNSCC. Many of these inhibitors have shown promise, while the effects of others are tempered by the mechanisms through which HNSCC can evade therapy. As such, current research aimed at elucidating the interactions between PI3K/Akt/mTOR and other important signaling pathways which may drive resistance in HNSCC, such as p53, NF-κB, and MAPK, has become a prominent focus toward better understanding how to most effectively treat HNSCC.

Keywords: Akt; NF-κB; PI3K; head and neck cancer; mTOR; p53.

Publication types

  • Review

MeSH terms

  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / metabolism
  • Genetic Variation
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / metabolism
  • Humans
  • Phosphatidylinositol 3-Kinase* / genetics
  • Phosphatidylinositol 3-Kinase* / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt* / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Receptor Cross-Talk
  • Signal Transduction
  • TOR Serine-Threonine Kinases* / antagonists & inhibitors
  • TOR Serine-Threonine Kinases* / genetics
  • TOR Serine-Threonine Kinases* / metabolism


  • Phosphoinositide-3 Kinase Inhibitors
  • MTOR protein, human
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases