Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center announced on Mar. 10 that lowering levels of a clotting protein called fibrinogen could slow the progression of pancreatic cancer in mice.
The findings are important because pancreatic ductal adenocarcinoma, a common form of pancreatic cancer, is known for its aggressive nature and poor prognosis, especially when it spreads to the liver. The study suggests that targeting fibrinogen may help reduce tumor growth and limit metastasis.
Melissa L. Fishel, PhD, who led the research team, said their experiments showed that depleting fibrinogen in mouse models resulted in smaller primary tumors and fewer liver metastases. "When fibrin was not there, we saw a dramatic reduction in primary tumor size as well as liver lesions," Fishel said. "When pancreatic cancer spreads to the liver the patient prognosis is grim, so we were very excited by the possibility of reducing that tumor burden and metastasis." She added, "Something about not having fibrin in the primary pancreatic tumor site really changes those tumor cells, so they are either less likely to leave the pancreas or are somehow unable to make a liver lesion."
Fishel explained that while fibrinogen is necessary for normal blood clotting, its levels are elevated in pancreatic cancer patients. "Since levels of fibrinogen are elevated in pancreatic cancer, the idea would be to return it to baseline - not to zero," she said. "We believe that could be clinically manageable."
The study used multiple methods to reduce fibrinogen and included tumor cell models derived from Indiana University patient samples. Researchers also tested whether circulating fibrin contributed to metastasis but found no difference in metastatic growth with or without circulating fibrinogen.
Looking ahead, Fishel said future research will focus on combining approaches that target fibrinogen with chemotherapy or other emerging therapies for pancreatic cancer since reducing fibrinogen delayed disease progression but did not cure it in mice. "Now we want to understand what fibrin is turning on or off in the tumor so we can combine treatments to make them more effective," she said.
The research was part of the Pancreatic Cancer Stromal Reprogramming Consortium, a national collaboration aimed at accelerating discoveries related to this disease.
