Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia syndrome delays its onset and prolongs survival

Francis Robert, John R. Mills, Aouod Agenor, Dantong Wang, Sergio DiMarco, Regina Cencic, Michel L. Tremblay, Imed Eddine Gallouzi, Siegfried Hekimi, Simon S. Wing, Jerry Pelletier

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25 Citations (Scopus)

Abstract

Anorexia-cachexia syndrome (ACS) is a major determinant of cancer-related death that causes progressive body weight loss due to depletion of skeletal muscle mass and body fat. Here, we report the development of a novel preclinical murine model of ACS in which lymphomas harbor elevated Myc and activated mTOR signaling. The ACS phenotype in this model correlated with deregulated expression of a number of cytokines, including elevated levels of interleukin-10 which was under the direct translational control of mTOR. Notably, pharmacologic intervention to impair protein synthesis restored cytokine production to near-normal levels, delayed ACS progression, and extended host survival. Together, our findings suggest a new paradigm to treat ACS by strategies which target protein synthesis to block the production of procachexic factors.

Original languageEnglish
Pages (from-to)747-756
Number of pages10
JournalCancer Research
Volume72
Issue number3
DOIs
Publication statusPublished - 1 Feb 2012

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Robert, F., Mills, J. R., Agenor, A., Wang, D., DiMarco, S., Cencic, R., Tremblay, M. L., Gallouzi, I. E., Hekimi, S., Wing, S. S., & Pelletier, J. (2012). Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia syndrome delays its onset and prolongs survival. Cancer Research, 72(3), 747-756. https://doi.org/10.1158/0008-5472.CAN-11-2739