Project 462003

There is strong evidence converging to the key role of cholesterol in pancreatic cancer. The development of a drug acting via the disturbance of cholesterol homeostasis (balance) seems very promising. Furthermore, these cholesterol based disturbance therapeutic approaches could provide selectivity of action for cancer cells over normal cells (less side effects), and could also provide a possibility of combination with other anticancer drugs acting by different mechanism of action (to counter drug resistance). The present project will focus on aminosteroid derivative RM-581, which shown promising results in Gemcitabine-resistant pancreatic cancer cells (PANC-1) and in mice with pancreatic tumors. No toxicity was also observed in mice. Our working hypothesis is that RM-581 or an analog is a novel drug candidate to treat pancreatic cancer, a disease with a very bad prognosis (only 8% of survival after 5 years). Various aspect of this new molecule (RM-581 or an analog) will be investigated including its mechanism of action (how it work) and its pharmaceutical translational potential with different pancreatic cancer models. Obviously the arrival of an efficient first-in-class drug is highly anticipated and would be very helpful to give a novel therapeutic option to pancreatic cancer patients.