Complete remission in advanced epithelial ovarian cancer is predicted by metabolic signatures measured in the media of patient's primary culture 3D tumor explants: A metabolomic analysis

Abstract Ovarian cancer is the leading cause of gynecologic cancer death with over 21,000 new diagnosis and 13,000 deaths each year in the US. Treatment with platinum-based chemotherapy induces remission in up to 80% of patients yet the majority relapse and die from their disease within 5 years. We recently reported the analysis of patients with advanced ovarian cancers using plasma metabolomics to predict response and survival (D’Amora et al Gynecol Oncol, October 2021). As part of that study human tumor explants were submitted for the measurement of platinum resistance by ex vivo analysis of programmed cell death (EVA/PCD࣪). Media obtained from the non-drug exposed control cultures were examined by mass spectrometry for the quantification of 186 individual metabolites using the Biocrates’ p180 platform. Results obtained with the tissue culture media identify biochemical signatures that correlate with the achievement of complete pathologic remission. Among the most discrimination findings were the media concentrations of phosphatidyl choline (PC) aa c42:0 and the ratio of (PC) aa C40:2 divided by (PC) ae C42:1 suggesting either hyperactivity of lipid elongases or defective beta oxidation of very long chain fatty acids in drug refractory patients. When we compared the results of 8 patients who achieved pCR with 3 patients with residual disease the aa C42:0 concentration and the ratio aa C42:0/ae C42:1 provided an AUC= 0.958 (p. < 0.01) The findings suggest that peroxisomal dysfunction leads to the accumulation of very long chain fatty acid lipids. These species are known to induce endoplasmic reticulum and oxidative stress and are associated with the neurodegenerative diseases like Zellweger syndrome. We have reported similar findings in drug refractory breast cancer patients (da Silva et al, Oncotarget, August Aug 2018) suggesting common lipid metabolic changes in drug resistant adenocarcinomas. The results of these analyses could provide prognostic and predictive information for patients diagnosed with advanced epithelial ovarian cancers. Further studies correlating these findings with plasma metabolic signatures are underway as will be reported. Citation Format: Adam J. Nagourney, Paulo D'Amora, Ismael Dale Cotrim Guerreiro Silva, Steven S. Evans, Robert A. Nagourney. Complete remission in advanced epithelial ovarian cancer is predicted by metabolic signatures measured in the media of patient’s primary culture 3D tumor explants: A metabolomic analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1965.