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Squamous cell Carcinoma pp 163–181Cite as

Targeting the mTOR Signaling Circuitry in Head and Neck Cancer

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Abstract

The recent development of deep-sequencing approaches for the study of human cancer represents a revolution in medical oncology. These approaches provide an unprecedented knowledge of the multiplicity of genomic and epigenetic alterations underlying each cancer type, and enable the elucidation of aberrant molecular networks driving tumor progression. The in-depth analysis of the head and neck cancer (HNSCC) oncogenome revealed that most HPV negative and HPV positive HNSCC lesions exhibit mutations and copy number alterations converging in the aberrant activation of the PI3K-mTOR pathway. In turn, this overreliance on PI3K-mTOR signaling for tumor growth can expose a cancer vulnerability that can be exploited for therapeutic purposes. Indeed, we have shown that the vast majority of HNSCC lesions exhibit highly active PI3K-mTOR pathway. Furthermore, we have shown that the administration of mTOR inhibitors causes tumor regression and prevents the malignant conversion of oral precancer lesions in multiple chemically induced and genetically defined HNSCC animal models. Many PI3K-mTOR pathway inhibitors have been recently advanced to the clinic with encouraging results in HNSCC. Overall, we can expect that the use of PI3K-mTOR inhibitors will provide an opportunity for precision medicine approaches for HNSCC prevention and treatment.

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Authors and Affiliations

  1. Department of Pharmacology, Moores Cancer Center, University of California San Diego (UCSD), San Diego, CA, 92093, USA

    Panomwat Amornphimoltham

  2. Bioinformatics and Systems Biology Program, University of California San Diego (UCSD), San Diego, CA, 92093, USA

    Samuel J. Roth

  3. Department of Medicine and Cancer Cell Map Initiative, University of California San Diego (UCSD), San Diego, CA, 92093, USA

    Trey Ideker

  4. Department of Pharmacology, Moores Cancer Center and Cancer Cell Map Initiative, University of California San Diego (UCSD), San Diego, CA, 92093, USA

    J. Silvio Gutkind

Authors
  1. Panomwat Amornphimoltham
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  2. Samuel J. Roth
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  3. Trey Ideker
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  4. J. Silvio Gutkind
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Corresponding author

Correspondence to J. Silvio Gutkind .

Editor information

Editors and Affiliations

  1. Oral Medicine, King's College London Oral Medicine, Surrey, United Kingdom

    Saman Warnakulasuriya

  2. Cedars-Sinai Medical Center, Department of Biomedical Sciences Cedars-Sinai Medical Center, Los Angeles, California, USA

    Zakir Khan

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Amornphimoltham, P., Roth, S.J., Ideker, T., Silvio Gutkind, J. (2017). Targeting the mTOR Signaling Circuitry in Head and Neck Cancer. In: Warnakulasuriya, S., Khan, Z. (eds) Squamous cell Carcinoma. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1084-6_7

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