Cosimo Commisso, PhD, and Susanne Heynen-Genel, PhD, have received a grant from the National Cancer Institute (NCI) to advance a new treatment approach for pancreatic cancer.
The four-year, $2.6 million project will identify potential drugs that can manipulate the pH of cells to stop pancreatic tumors from growing. The promising approach would selectively kill pancreatic cancer cells without affecting surrounding healthy cells.
“Pancreatic cancer is a growing global health crisis, and there is an urgent need for better ways to treat it,” says Commisso, an associate professor at Sanford Burnham Prebys. “This project will help us find molecules that are the starting points to create new medicines.”
Pancreatic cancer accounts for just 3% of cancer cases in the United States, but it is so difficult to treat that it is projected to become the second-leading cause of cancer-related death by 2030. According to the NCI, about 49,830 people died from pancreatic cancer in the United States in 2022.
“Pancreatic cancer tends to be diagnosed late, because it’s an organ lying deep in the body and can grow undetected for years,” says Commisso. “Since I started working in this field more than a decade ago, we’ve managed to double the survival rates for people with pancreatic cancer. But that’s not good enough—the five-year survival rate after diagnosis is only around 10%.”
Commisso and his team discovered that pancreatic cancer cells have a unique way of regulating their pH—a measure of acidity. Cells need to maintain a pH within a certain range to survive and grow. Pancreatic cancer cells control their pH by packaging up excess acid and storing it separately from the rest of the cell’s fluids. This process doesn’t occur in healthy cells.
“One really promising aspect of this approach is that once we find the right drug, we’ll be able to kill the cancer cells without causing any damage to the rest of the body,” says Commisso. “Metabolic approaches like this are the future of targeted cancer therapy.”
Transforming Commisso’s discoveries into a real medicine will require the drug discovery capabilities of Heynen-Genel and her team at the Conrad Prebys Center for Chemical Genomics.
“This is such an important grant because it supports the first steps toward translating this novel discovery into a new treatment that could give hope to so many people with pancreatic cancer,” says Heynen-Genel. “This grant helps us lay the groundwork to figure out how this research could be applied in the clinic.”
The researchers will screen hundreds of thousands of molecules and identify a select few “hits” that have desirable biological effects and chemical properties. Then they will conduct other studies on these hits to see which have the most potential to fight pancreatic cancer with minimal side effects. By the end of the grant, the team will have several drug candidates that can be developed further toward anticancer therapies.
“We could find the next major breakthrough in pancreatic cancer treatment, but we have to put in the legwork now to find out,” says Heynen-Genel. “That’s what’s exciting about drug discovery. It feels like it has infinite potential.”
The title of the grant, issued by the National Cancer Institute of the National Institutes of Health, is “Discovery of Novel Inhibitors Targeting trans-Golgi Network Acidification in Pancreatic Cancer” (R01 CA276193)