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The PI3K Signaling Pathway in Head and Neck Squamous Cell Carcinoma

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Molecular Determinants of Head and Neck Cancer

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

The PI3K/PTEN/AKT/mTOR signaling axis has been intensively studied in many cancer systems. Current evidence suggests deregulation of this pathway plays a unique 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. Yet, PI3K/PTEN/AKT/mTOR signaling has an intimate 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. We will also discuss differences in PI3K/PTEN/AKT/mTOR signaling with respect to HPV status. A number of inhibitors targeting multiple nodes in this pathway have been developed as agents have broad application across many cancer types. We will briefly review how these therapeutic agents are being evaluated and what predictive biomarkers have been established in HNSCC for these drugs. Finally, PI3K/PTEN/AKT/mTOR signaling represents an important source of resistance to radiation, chemotherapy, and other targeted agents. We will also speculate on how PI3K/PTEN/AKT/mTOR inhibitors may increase the efficacy of these established therapies. Although PI3K/PTEN/AKT/mTOR investigations are relatively new to HNSCC research, early evidence suggests further evaluation of this essential signal transduction pathway is warranted.

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Authors and Affiliations

  1. Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins Medical Institute, 21231, Baltimore, MD, USA

    Jason D. Howard PhD

  2. Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins Medical Institute, 1650 Orleans Street, CRB-1 rm. 344, 21231, Baltimore, MD, USA

    Christine H. Chung MD

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Correspondence to Christine H. Chung MD .

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  1. Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Barbara Burtness

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

    Erica A. Golemis

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Howard, J., Chung, C. (2014). 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. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8815-6_7

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