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Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
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The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, cross-talk, and therapies

R Vander Broek1,2,3, S Mohan1,2, D F Eytan1,2

  • 1Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA.

Oral Diseases
|November 14, 2013
PubMed

Insights

Alterations in the PI3K/Akt/mTOR pathway are common in head and neck squamous cell carcinoma (HNSCC). Research is exploring targeted therapies and resistance mechanisms for improved HNSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is a genetically diverse and aggressive malignancy.
  • The PI3K/Akt/mTOR pathway is frequently altered in HNSCC, regulating critical cellular functions like survival and metabolism.
  • These pathway alterations contribute to HNSCC development and progression.

Purpose of the Study:

  • To investigate the role of the PI3K/Akt/mTOR pathway in HNSCC.
  • To review the development and clinical investigation of PI3K/Akt/mTOR inhibitors for HNSCC.
  • To explore signaling pathways that mediate therapeutic resistance in HNSCC.

Main Methods:

  • Review of genetic aberrations (mutations, copy number variations) and expression dysregulation in the PI3K/Akt/mTOR pathway in HNSCC.
  • Analysis of preclinical and clinical studies on PI3K, Akt, and mTOR inhibitors in HNSCC.
  • Examination of research on interactions between PI3K/Akt/mTOR and other pathways (p53, NF-κB, MAPK) driving resistance.

Main Results:

  • Consistent alterations in the PI3K/Akt/mTOR pathway are observed across most HNSCC cases.
  • Numerous PI3K/Akt/mTOR inhibitors are under active preclinical and clinical investigation for HNSCC.
  • Therapeutic efficacy is often limited by HNSCC's ability to evade treatment through various resistance mechanisms.

Conclusions:

  • Targeting the PI3K/Akt/mTOR pathway is a promising strategy for HNSCC treatment.
  • Understanding resistance mechanisms involving pathways like p53, NF-κB, and MAPK is crucial for optimizing HNSCC therapy.
  • Further research into pathway interactions is essential for developing more effective HNSCC treatments.
Keywords:
AktNF-κBPI3Khead and neck cancermTORp53

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