Authors

Anthony D Saleh, Radiation Oncology Brach, National Cancer Institute, National Institutes of Health
Brittany A Simone, Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson UniversityFollow
Juan Palazzo, Department of Pathology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson UniversityFollow
Jason E Savage, Radiation Oncology Brach, National Cancer Institute, National Institutes of Health
Yuri Sano, Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University
Tu Dan, Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson UniversityFollow
Lianjin Jin, Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson UniversityFollow
Colin E Champ, Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson UniversityFollow
Shuping Zhao, Radiation Oncology Brach, National Cancer Institute, National Institutes of Health
Meng Lim, Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson UniversityFollow
Frederica Sotgia, Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University
Kevin Camphausen, Radiation Oncology Brach, National Cancer Institute, National Institutes of Health
Richard G Pestell, Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
James B Mitchell, Radiation Biology Branch, National Cancer Institute, National Institutes of Health
Michael P Lisanti, Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Nicole L Simone, Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

6-15-2013

Comments

This article has been peer reviewed. It was published in: Cell Cycle.
Volume 12, Issue 12, 15 June 2013, Pages 1955-1963.
The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735710/. DOI: 10.4161/cc.25016

Copyright © 2013 Landes Bioscience.

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 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.

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