Dissecting the Akt/mammalian target of rapamycin signaling network: Emerging results from the head and neck cancer tissue array initiative

Alfredo A. Molinolo, Stephen M. Hewitt, Panomwat Amornphimoltham, Somboon Keelawat, Samraeung Rangdaeng, Abelardo Meneses García, Ana R. Raimondi, Rafael Jufe, María Itoiz, Yan Gao, Dhananjaya Saranath, George S. Kaleebi, George H. Yoo, Lee Leak, Ernest M. Myers, Satoru Shintani, David Wong, H. Davis Massey, William Andrew Yeudall, Fulvio LonardoJohn Ensley, J. Silvio Gutkind

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma. Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array. Results: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently fromthe activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR. Conclusions:These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.

Original languageEnglish (US)
Pages (from-to)4964-4973
Number of pages10
JournalClinical Cancer Research
Volume13
Issue number17
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Molinolo, A. A., Hewitt, S. M., Amornphimoltham, P., Keelawat, S., Rangdaeng, S., García, A. M., Raimondi, A. R., Jufe, R., Itoiz, M., Gao, Y., Saranath, D., Kaleebi, G. S., Yoo, G. H., Leak, L., Myers, E. M., Shintani, S., Wong, D., Massey, H. D., Yeudall, W. A., ... Gutkind, J. S. (2007). Dissecting the Akt/mammalian target of rapamycin signaling network: Emerging results from the head and neck cancer tissue array initiative. Clinical Cancer Research, 13(17), 4964-4973. https://doi.org/10.1158/1078-0432.CCR-07-1041