Targeting metabolic pathways to radiosensitize pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer related mortality killing 117 PC patients every day in the United States. The efficacy of systemic chemotherapy and radiotherapy (RT) is tempered by the acquired and innate therapeutic resistance resulting in limited survival benefits to PDAC patients. Our bioinformatics and high throughput database analysis revealed that cholesterol biosynthesis (CBS) pathway is involved in radioresistance of PC patients. We have shown previously that Zoledronic acid (ZOL), a specific inhibitor of FDPS, induces radiosensitivity. In this study we explore the transcriptional regulation and mechanisms underlying its radiosensitization.