Grant bolsters pancreatic cancer drug discovery

Vanderbilt. US: The Lustgarten Foundation has awarded a $1.5 million Research Investigator Grant to Stephen Fesik, Ph.D., professor of Biochemistry, Pharmacology and Chemistry, for research designed to discover new drugs for the treatment of pancreatic cancer. This is Fesik’s second three-year award from the Lustgarten Foundation in support of his research targeting K-Ras, a protein mutated in 90 percent of pancreatic cancer cases, as well as other forms of cancer.Fesik is among 13 scientists nominated by their peers for significant achievements in the field of pancreatic cancer research who will receive a total of $19.5 million in research funding from the foundation.

“I am very happy to receive this award. This will greatly help our efforts in targeting this horrible disease,” said Fesik, Orrin H. Ingram II Professor of Cancer Research and co-leader of the Signal Transduction and Chemical Biology Research Program.
The pancreas is an organ located deep in the abdomen between the stomach and the spine. It produces juices containing enzymes that help digest food and also serves as a gland that produces insulin. Since pancreatic cancer may cause no obvious symptoms in its earliest stages, the disease is often diagnosed when the cancer is already advanced. Only 6 percent of patients are still alive five years after diagnosis, making pancreatic cancer one of the most deadly forms of cancer.
The K-Ras protein controls many processes that are important for tumor cell growth, but it is a challenging protein to target and has been considered undruggable.
Fesik and his colleagues recently discovered small molecules that affect the function of K-Ras by binding to a regulatory protein (SOS) responsible for activating K-Ras. In preliminary testing, the molecules kill cancer cells by inhibiting Ras signaling.
“We do not yet understand why these small molecules function in this manner and the compounds are not currently potent enough for use as pharmaceutical agents. Nevertheless, they represent a promising starting point for discovering more potent compounds that inhibit K-Ras function and could be used to treat pancreatic and other Ras-driven types of cancer,” Fesik said.
He and his colleagues plan to study the mechanism of action of the compounds and optimize them to inhibit K-Ras signaling and kill pancreatic tumor cells. In the future, they also plan to examine the ability of their compounds to shrink pancreatic cancer tumors in animal studies.
Fesik is a fellow of the American Association for the Advancement of Science (AAAS). In 2010, he received the National Institutes of Health (NIH) Director’s Pioneer Award for his efforts to revolutionize the process of drug discovery. He has also received the Lifetime Achievement Award in Nuclear Magnetic Resonance from the Eastern Analytical Society as well as the SBS Technology Innovation Award.
The Lustgarten Foundation is a nonprofit organization dedicated to promoting research that will lead to a cure for pancreatic cancer. Inspired by Marc Lustgarten, vice chair of Cablevision and chair of Madison Square Garden in New York City, the foundation was launched in 1999.
Lustgarten, who served on the initial board of directors for the foundation, died from pancreatic cancer at 52.