| Timetable |
| Download Conference Program |
| Download All Abstracts |
| Zoom Access |
| Corporate Program |
Poster Presentations
Day 4, June 25（Wed.）
Room P (Maesato East, Foyer, Ocean Wing)
- 4P-PM-23
Repurposing Statins Induces Metabolic Reprogramming and Triggers Ferroptotic Regression in KRAS-Mutant Colorectal Cancer
(HKBU)
oJieqing Feng, Hong Yan, Zongwei Cai
Colorectal cancer (CRC) ranks third in global cancer prevalence, and -50% of CRC patients harbor KRAS variants at codon 12 and 13<SUP>. KRAS-directed therapies are challenging due to KRAS protein structure, leading to an unmet need to repurpose effective treatment options for CRC patients. Aberrant lipid biosynthesis is required for cancer cells to reduce lipid peroxidation production and avoid ferroptotic programmed cell death. Peroxisome proliferator-activated receptor-γ (PPARγ) is involved in lipid homeostasis maintenance, and PPARγ activation show anti-proliferative effects<SUP>. HMG-CoA reductase inhibitors (statins) are shown to activate PPARγ in various cells, indicating statins may be promising drugs for CRC treatment. This study repurposes eight statins to inhibit lipid synthesis, and six statins sensitize CRC cells to undergo ferroptosis, showing profound anti-cancer activity. Metabolic results show statins significantly upregulate the putrescine, γ-glutamylcysteine, and glucose but maintain the spermidine and spermine levels, and decrease glutathione, glutathione disulfide, and glucose 6-phosphate in glutaminolysis and glycolysis pathways. RNA-seq data from human CRC reveal lower expression of key enzymes (spermidine synthase, glutathione synthetase, hexokinase 1 and 2) in corresponding pathways predicts better overall survival. These results indicate statin-induced metabolic reprogramming creates a therapeutic vulnerability of CRC by promoting ferroptotic cell death.