OXFORD, Miss. – Aggressive cancers can use blood vessels like roadways, speeding through the body and finding new places to grow. But new research shows that a drug in clinical trials may help stop the spread of cancer before it reaches its destination.
University of Mississippi research shows that ifetroban, an anti-platelet drug, can help the immune system better identify and remove cancer cells that have entered the bloodstream. Stopping metastasis, the process by which cancers spread, would take the teeth out of aggressive diseases such as breast, lung and pancreatic cancers.
“The spread of cancer is what kills people,” said Thomas Werfel, associate professor of biomedical engineering. “We can treat local cancer – it’s the metastatic cancer that’s really devastating, and that’s what we’re targeting.”
When cancer cells enter the bloodstream, they form bonds with blood platelets, effectively creating a “shield” around the cancer cell that hides it from white blood cells and other agents of the immune system. Ifetroban stops those platelet bonds from forming, which allows the immune system to target and remove cancer cells before they spread to a new location.
“Once cancer enters the metastatic stage, survivability goes way down,” said Veeresh Toragall, postdoctoral researcher in the Department of Biomedical Engineering. “What we are thinking is that we target the metastasis, the spread of cancer. In this case, what we have done is a very simple thing: we have reduced the interaction between the platelets and the tumor cells.
“Once you take out the interaction between these two, the platelets are no longer safeguarding the circulating tumor cells in the body. So, the body’s immune system is free to attack these tumor cells and remove them.”
The study, published in Experimental Hematology and Oncology, tested ifetroban’s ability to stop platelet shielding in triple-negative breast cancer, a particularly aggressive disease that accounts for 1 in 10 breast cancer diagnoses.Previous studies have shown that triple-negative breast cancer is associated with higher activity of TPr, a receptor that helps platelets stick to tumor cells.
“So, the question was, how effective would it be to target TPr and block it?” Werfel said. “We know that TNBC is a very metastatic disease, and it made sense for us to try to reduce metastasis as a way to reduce mortality.”
The study showed ifetroban reduced lung metastases by 67%, liver metastases by 60% in animal models and reduced overall circulating tumor cells by more than 50%.
“Right now, there are very few – if any – drugs that are approved to specifically target metastasis,” Werfel said. “This is not going to replace other cancer drugs. You’re still going to want cytotoxic therapy to kill the cancer cells.
“But while you’re killing them, you know they’re not going to other places and creating new tumors.”
Because ifetroban has already been tested for safety in more than 1,400 patients in previous clinical trials, it could become a cancer therapy much more quickly than traditional drug-discovery timelines.
“This drug has already been studied for other uses and it’s in clinical trials right now,” Toragall said. “This shortens the timeline to approval for the treatment of cancer metastasis.
“We won’t have to wait 15 years to get this on the market if it’s found to be safe and effective in cancer clinical trials.”
This material is based on work supported by the American Cancer Society grant nos. RSG-21-114-01-MM to TW and by the National Institutes of Health grant no. P20 GM104357. The research was conducted in collaboration with the University of Mississippi Medical Center and supported by Cumberland Pharmaceuticals, which provided the investigational drug ifetroban.
