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The PI3K Signaling Pathway in Head and Neck Squamous Cell Carcinoma

  • Alexander Y. Deneka
  • Jason D. Howard
  • Christine H. Chung
Chapter
Part of the Current Cancer Research book series (CUCR)

Abstract

The PI3K/PTEN/AKT/mTOR signaling axis has been intensively studied in many cancer systems. Extensive evidence suggests deregulation of this pathway plays an important role in the initiation, development, and recurrence of head and neck squamous cell carcinoma (HNSCC). A heterogeneous disease by nature, HNSCC encompasses a disparate collection of anatomical sites with complex tumor biology. Nevertheless, PI3K/PTEN/AKT/mTOR signaling has a critical role in nearly every facet of this disease. In this chapter we will provide a brief introduction to the mechanisms involved in PI3K/PTEN/AKT/mTOR signaling and how specific alterations in these signaling nodes enable HNSCC development and progression. We will also discuss differences in PI3K/PTEN/AKT/mTOR signaling with respect to human papillomavirus (HPV) status. A number of inhibitors targeting multiple nodes in this pathway have been developed, with these agents having potential application and in some cases demonstrated clinical activity in HNSCC. We will briefly review how these therapeutic agents are being evaluated and what predictive biomarkers have been established for them in HNSCC. Finally, PI3K/PTEN/AKT/mTOR signaling represents an important source of resistance to radiation and chemotherapy as well as other targeted agents. We will speculate on how PI3K/PTEN/AKT/mTOR inhibitors may increase the efficacy of these established therapies.

Keywords

PI3K PTEN AKT mTOR HPV HNSCC Biomarkers 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Alexander Y. Deneka
    • 1
    • 2
  • Jason D. Howard
    • 3
  • Christine H. Chung
    • 3
    • 4
  1. 1.Molecular Therapeutics Program, Fox Chase Cancer CenterPhiladelphiaUSA
  2. 2.Kazan Federal UniversityKazanRussia
  3. 3.Department of OncologySidney Kimmel Cancer Center, Johns Hopkins Medical InstituteBaltimoreUSA
  4. 4.Department of Head and Neck-Endocrine OncologyMoffitt Cancer CenterTampaUSA

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