Caloric restriction augments radiation efficacy in breast cancer.

Published

Journal Article

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 mTOR 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.

Full Text

Duke Authors

Cited Authors

  • Saleh, AD; Simone, BA; Palazzo, J; Savage, JE; Sano, Y; Dan, T; Jin, L; Champ, CE; Zhao, S; Lim, M; Sotgia, F; Camphausen, K; Pestell, RG; Mitchell, JB; Lisanti, MP; Simone, NL

Published Date

  • June 15, 2013

Published In

Volume / Issue

  • 12 / 12

Start / End Page

  • 1955 - 1963

PubMed ID

  • 23708519

Pubmed Central ID

  • 23708519

Electronic International Standard Serial Number (EISSN)

  • 1551-4005

Digital Object Identifier (DOI)

  • 10.4161/cc.25016

Language

  • eng

Conference Location

  • United States