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

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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

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Sirolimus
Head and Neck Neoplasms
Epidermal Growth Factor Receptor
Phospho-Specific Antibodies
Critical Pathways
Squamous Cell Carcinoma
Research Design
Carcinoma, squamous cell of head and neck
Biopsy
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Molinolo, A. A., Hewitt, S. M., Amornphimoltham, P., Keelawat, S., Rangdaeng, S., García, A. M., ... 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

Dissecting the Akt/mammalian target of rapamycin signaling network : Emerging results from the head and neck cancer tissue array initiative. / Molinolo, Alfredo A.; Hewitt, Stephen M.; Amornphimoltham, Panomwat; Keelawat, Somboon; Rangdaeng, Samraeung; García, Abelardo Meneses; Raimondi, Ana R.; Jufe, Rafael; Itoiz, María; Gao, Yan; Saranath, Dhananjaya; Kaleebi, George S.; Yoo, George H.; Leak, Lee; Myers, Ernest M.; Shintani, Satoru; Wong, David; Massey, H. Davis; Yeudall, William Andrew; Lonardo, Fulvio; Ensley, John; Gutkind, J. Silvio.

In: Clinical Cancer Research, Vol. 13, No. 17, 01.09.2007, p. 4964-4973.

Research output: Contribution to journalArticle

Molinolo, AA, Hewitt, SM, Amornphimoltham, P, Keelawat, S, Rangdaeng, S, García, AM, Raimondi, AR, Jufe, R, Itoiz, M, Gao, Y, Saranath, D, Kaleebi, GS, Yoo, GH, Leak, L, Myers, EM, Shintani, S, Wong, D, Massey, HD, Yeudall, WA, Lonardo, F, Ensley, J & Gutkind, JS 2007, 'Dissecting the Akt/mammalian target of rapamycin signaling network: Emerging results from the head and neck cancer tissue array initiative', Clinical Cancer Research, vol. 13, no. 17, pp. 4964-4973. https://doi.org/10.1158/1078-0432.CCR-07-1041
Molinolo, Alfredo A. ; Hewitt, Stephen M. ; Amornphimoltham, Panomwat ; Keelawat, Somboon ; Rangdaeng, Samraeung ; García, Abelardo Meneses ; Raimondi, Ana R. ; Jufe, Rafael ; Itoiz, María ; Gao, Yan ; Saranath, Dhananjaya ; Kaleebi, George S. ; Yoo, George H. ; Leak, Lee ; Myers, Ernest M. ; Shintani, Satoru ; Wong, David ; Massey, H. Davis ; Yeudall, William Andrew ; Lonardo, Fulvio ; Ensley, John ; Gutkind, J. Silvio. / Dissecting the Akt/mammalian target of rapamycin signaling network : Emerging results from the head and neck cancer tissue array initiative. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 17. pp. 4964-4973.
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AU - Amornphimoltham, Panomwat

AU - Keelawat, Somboon

AU - Rangdaeng, Samraeung

AU - García, Abelardo Meneses

AU - Raimondi, Ana R.

AU - Jufe, Rafael

AU - Itoiz, María

AU - Gao, Yan

AU - Saranath, Dhananjaya

AU - Kaleebi, George S.

AU - Yoo, George H.

AU - Leak, Lee

AU - Myers, Ernest M.

AU - Shintani, Satoru

AU - Wong, David

AU - Massey, H. Davis

AU - Yeudall, William Andrew

AU - Lonardo, Fulvio

AU - Ensley, John

AU - Gutkind, J. Silvio

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