Abstract 4062: Activity of 3 Bromopyruvate in human tumor primary culture 3-dimensional explants using ex vivo analysis of programmed cell death

Altered metabolism is a hallmark of human malignancy. The “Warburg Effect “reflecting increased glycolytic activity in the presence of oxygen represents an opportunity to target specific features of cancer to induce selective toxicity to malignantly transformed cells. 3-bromopyruvate (3-BP) is a pyruvate analogue that inhibits hexokinase II at the mitochondrial level resulting in cancer cell death. Numerous studies have confirmed activity for 3-BP in human SW480 and HT 29 colon carcinoma, glioblastoma (U373MG), HTP-1 leukemic and other cell lines. Our interest in exploring the activity of 3-BP in human tumor primary culture explants led to the application of the ex vivo analysis of programmed cell death in 19 patient tumors. The intent was to develop concertation ranges for future studies and explore disease-specific activity. Methods: Fresh Sterile tumor samples were mechanically and enzymatically disaggregated and 3-dimensional organoids of desired size isolated by density centrifugation. Blood samples were isolated by density centrifugation. Cell suspensions in modified RPMI media were exposed to serial dilutions of 3-BP for 72 hours and then assessed for cell death by morphology, staining characteristics and ATP content by luciferase. Viability was scored against saline-exposed controls, normalized to 100%. Results: 3BP reveals activity in human tumor explants. Activity varied by cancer type. Hematologic tumors including NHL, CLL and AML were found sensitive as were several solid tumors including GI and lung cancers. Of interest lower degrees of activity were observed in breast and ovarian cancers that are generally considered chemo-sensitive . Activity in 2 fibrolamellar cancers could suggest a novel therapy for this drug refractory neoplasm. Studies are underway examining 3-BP correlations with other classes of drugs and metabolic inhibitors as well as 3-BP combinatorial potential. Supported by the Fibro fighters Foundation Citation Format: Adam Jeremiah Nagourney, Paulo D'Amora, Steven Scott Evans, Paula Bernard, Federico Francisco, Young Ko, Thomas Stockwell, Maxine Johnson, Robert Alan Nagourney. Activity of 3 Bromopyruvate in human tumor primary culture 3-dimensional explants using ex vivo analysis of programmed cell death [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 4062.