title: Caloric restriction augments radiation efficacy in breast cancer.
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.
authors.affiliation: Radiation Oncology Brach, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Saleh
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Simone
authors.forename: Juan
authors.initials: J
authors.lastname: Palazzo
authors.forename: Jason E
authors.initials: JE
authors.lastname: Savage
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sano
authors.forename: Tu
authors.initials: T
authors.lastname: Dan
authors.forename: Lianjin
authors.initials: L
authors.lastname: Jin
authors.forename: Colin E
authors.initials: CE
authors.lastname: Champ
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhao
authors.forename: Meng
authors.initials: M
authors.lastname: Lim
authors.forename: Frederica
authors.initials: F
authors.lastname: Sotgia
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Simone
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D031204:Caloric Restriction; D045744:Cell Line, Tumor; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017526:Receptor, IGF Type 1
keywords: IGF; breast cancer; caloric restriction; cytotoxic therapy; radiation; tumor regression