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Molecular Determinants of Head and Neck Cancer pp 117–154Cite as

The PI3K Signaling Pathway in Head and Neck Squamous Cell Carcinoma

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Part of the book series: Current Cancer Research ((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.

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Authors and Affiliations

  1. Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA

    Alexander Y. Deneka

  2. Kazan Federal University, Kazan, Russia

    Alexander Y. Deneka

  3. Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins Medical Institute, Baltimore, MD, USA

    Jason D. Howard & Christine H. Chung

  4. Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Christine H. Chung

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  1. Alexander Y. Deneka
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Correspondence to Alexander Y. Deneka .

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Editors and Affiliations

  1. Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

    Barbara Burtness

  2. Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Erica A. Golemis

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Deneka, A.Y., Howard, J.D., Chung, C.H. (2018). The PI3K Signaling Pathway in Head and Neck Squamous Cell Carcinoma. In: Burtness, B., Golemis, E. (eds) Molecular Determinants of Head and Neck Cancer. Current Cancer Research. Humana Press, Cham. https://doi.org/10.1007/978-3-319-78762-6_5

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