Caloric restriction augments radiation efficacy in breast cancer

Anthony D. Saleh, Brittany A. Simone, Juan Palazzo, Jason E. Savage, Yuri Sano, Tu Dan, Lianjin Jin, Colin Champ, Shuping Zhao, Meng Lim, Frederica Sotgia, Kevin Camphausen, Richard G. Pestell, James B. Mitchell, Michael P. Lisanti, Nicole L. Simone

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories provided more significant tumor regression than alternate day feeding. At the molecular level, tumors treated with CR and IR showed less proliferation and more apoptosis. cDNA array analysis demonstrated the IGF-1R pathway plays a key role in achieving this physiologic response, and multiple members of the IGF-1R pathway including IGF-1R, IRS, PIK3ca and mTO R were found to be downregulated. The innovative use of CR as a novel therapeutic option has the potential to change the biology of tumors and enhance the opportunity for clinical benefit in the treatment of patients with TNBC.

Original languageEnglish (US)
Pages (from-to)1955-1963
Number of pages9
JournalCell Cycle
Volume12
Issue number12
DOIs
StatePublished - Jun 15 2013

Keywords

  • Breast cancer
  • Caloric restriction
  • Cytotoxic therapy
  • IGF
  • Radiation
  • Tumor regression

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Caloric restriction augments radiation efficacy in breast cancer'. Together they form a unique fingerprint.

Cite this