Metabolomics Profiles Suggest a Mechanism for Caloric Restriction Induced Radiation Sensitivity Kamila Nowak, MD, T. Dan, MD, C. Guha, MD, BA Simone, DO, L. Norton, MD, AP Dicker, MD PhD, N Simone, MD, I Kurland, MD PhD Department of Radiation Oncology, Kimmel Cancer Center, Thomas Jefferson University Caloric Restriction Augments Radiation: via What Mechanism? In multiple aggressive in vivo triple negative breast cancer models, our laboratory has shown that caloric restriction augments radiation effects Metabolomic profiling was performed to see if a biologic correlate could be identified for different treatment groups Control, Radiation (IR), Caloric Restriction (CR), and CR+IR Biocrates p180 kit used to assess metabolomic signature of treatment groups CR+IR causes less tumor growth and increased overall survival MetaboliteFunctions Polyamines spermine and spermidine ROS scavenger ArginineNitric oxide precursor C4:1-DC Acyl carnitineImplicated in breast cancer Lipids - LysoPC C20:3, Sphingomyelin (OH) C24:1 Implicated in breast cancer Metabolites contributing to most variance among different treatment groups Metabolic Profiles Clustered by Treatment Regimen Profiles were analyzed to determine differential patterns of response Patterns clustered by: Treatment regimen Early and late time points Early: 28 daysLate: 40 days Spermine and Spermidine Levels Following Treatment Metabolic profiles were distinct by treatment group Caloric restriction dampened the increased the increase in polyamines following radiation Given the role of polyamines as ROS scavengers, this may represent a radiosensitizing effect of radiation. Polyamines exhibit significant alteration in levels following treatment