Two Phospho-Compounds for Pancreatic Cancer Prevention

? DESCRIPTION (provided by applicant): Pancreatic cancer (PC) is a highly aggressive cancer with a dismal 5-year survival rate of < 5%. Current systemic standard chemotherapies provide marginal benefits to the patient, only prolonging survival for few weeks. Hence, developing novel preventive strategies for PC assume increase importance, with the development of novel chemopreventive agents being the most critical component. We propose to study two novel agents [phospho-valproic acid (P-V) and phospho-aspirin (P-A)], as a new drug combination for PC prevention. Recently, we showed that P-V strongly inhibits PC growth in multiple preclinical models of PC (up to 97% reduction compared to controls. P-V is safe, as shown by genotoxicity and animal toxicity studies, and mitochondrial STAT3 is its key molecular target. On the other hand, P-A is a strong inhibitor of EGFR activation and reduces PC xenograft growth by 78% compared to control. Remarkably, when given in combination, P-A and P-V prevented the development of pancreatic carcinoma by 95% (p