New drug Metavert blocks growth of pancreatic cancer in mice

The study, led by non-profit health science centre Cedars-Sinai, also demonstrated in mice that the drug, called Metavert, may prevent patients from developing a resistance to currently used pancreatic cancer chemotherapies.

Commenting on the potential impact of their findings, study lead author Mouad Edderkaoui PhD, assistant professor of Medicine and Biomedical Sciences at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai, said: “This is an exciting step toward improving survival rates in pancreatic cancer patients.  

Pancreatic cancer is the third-leading cause of cancer-related death in the United States, according to the American Cancer Society. This year, around 55,000 people in the U.S. will be diagnosed with the disease and more than 44,000 will die, making it one of the most deadly cancers. The pancreatic cancer five-year survival rate is only 7%.

95% of pancreatic cancer patients are diagnosed with PDAC, which develops from cells that line small tubes in the pancreas. PDAC can be difficult to treat because the cancer cells prompt normal cells that reside in the pancreas – called stellate cells – to produce pancreatic scar tissue. Scar tissue makes it difficult for chemotherapy agents and blood to enter the pancreas, explained the senior author of the study, Stephen J. Pandol MD, director of Basic and Translational Pancreas Research at Cedars-Sinai.

The cancer-stellate cell interaction also creates an environment that stimulates local tumour growth as well as cancer that spreads to distant sites in the body, said Pandol, a professor of Medicine at Cedars-Sinai. Additionally, the activity levels of certain enzymes increase significantly, which fuels resistance to cancer treatments.

“I’ve seen patients who respond to therapy for a while, and then the disease takes off because the cancer becomes smart – it blocks chemotherapy from working,” Pandol said. “Metavert targets that action.”

Over a four-year period, the investigators designed and synthesised new chemicals that inhibit cancer cell activity. They discovered that Metavert blocked drug resistance and also significantly boosted the positive effects of radiation and two chemotherapy agents commonly used in humans. In one of the mouse studies, Metavert increased the survival rate by about 50%.

According to Pandol, the investigators are currently developing a version of the drug to test in humans.

The study was published in the journal Gastroenterology.