Abstract 4900: Dynamic metabolic response of prostate cancer patients treated with ADT and low carb diet

Abstract

Abstract Background: Prostate cancer (PrCa) is one of the most common cancers among men and managed through surgery, hormonal therapy, chemotherapy, radiation, and cryotherapy. Depending on the stage of PrCa, androgen deprivation therapy (ADT) is commonly utilized as an intervention. ADT has proven effective in intervening in PrCa progression, although there are several side effects. Recently, the use of low carb diets has been shown to alter patients’ metabolic phenotype and as such may reduce the side effects of ADT. Methods: In this study 35 men, who were beginning ADT, were randomized to low carb diet intervention with recommended exercise or control (no lifestyle change) for 6 months. Primary results have been reported showing significant weight loss at both 3-month (17lb, p<0.01) and 6-month (23 lbs, p<0.01) and improved insulin control at 3-month (HOMA=-19 as compared to baseline, p=0.02) but not at 6-month (HOMA=-4 as compared to baseline, p=0.13). For this exploratory analysis, sera collected at baseline, 3, and 6 months was used for metabolomics analysis utilizing GC/MS TOF, QqQ LC-HILIC-MS/MS, and TripleTOF 6600 LC-RP-MS and lipidomics analysis using TripleTOF 5600+ MS/MSALL workflows to quantify the chemical diversity of the metabolome and lipidome. Results: Over 450 metabolites and 1000 lipid species were quantified. Metabolomics analysis of sera from the control patients (ADT alone) demonstrated alterations in steroid biosynthesis, androgen/estrogen metabolism, fatty acid metabolism, and lysine degradation. Lipidomics analysis of the control patients demonstrated changes in selective long chain polyunsaturated phosphatidylcholine species. Analysis of the ADT plus low carb patients revealed a change in pyruvate, glucose-alanine cycle, selenoamino acid, phenylalanine/tyrosine, and taurine metabolism. Further, lipidomic analysis revealed changes in several triglycerides, plasmalenylethanolamine, and phosphatidic acid species. Conclusion: In summary, integration of metabolomic and lipidomic analysis in hormonal and metabolic interventions of PrCa patients revealed dynamic changes providing novel insight for tailoring therapeutic intervention and monitoring. Citation Format: Stephen Freedland, Pao-Hwa Lin, Emily Y. Chen, Vladimir Tolstikov, Jen-Tsan Chi, Rangaprasad Sarangarajan, Niven R. Narain, Michael A. Kiebish. Dynamic metabolic response of prostate cancer patients treated with ADT and low carb diet [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4900.