Warfarin could be repurposed as a potent cancer drug

Warfarin

A new study has shown that blood thinner warfarin could also treat cancer, as it stops tumours from interfering with a self-destruct mechanism that cells initiate when they detect mutations or other abnormalities (ferroptosis).

The research by Columbia University researchers was conducted in human cells and in mice to uncover molecular processes that regulate ferroptosis.

“Our findings suggest that warfarin, which is already approved by the FDA, could be repurposed to treat a variety of cancers, including pancreatic cancer,” said study leader Wei Gu, the Abraham and Mildred Goldstein Professor of Pathology & Cell Biology (in the Institute for Cancer Genetics) at Columbia University Vagelos College of Physicians and Surgeons.

When the researchers performed genetic screens on human melanoma cells to identify genes that contribute to ferroptosis, they found that VKORC1L1 is a potent inhibitor of ferroptosis. Patients with low levels of VKORC1L1 activity generally lived longer than patients with higher levels.

The scientists found that warfarin, a known VKORC1L1 inhibitor, sensitised human pancreatic cancer cells to ferroptosis and strongly repressed tumour growth in a mouse model of pancreatic cancer.

Warfarin and other anticoagulants are commonly given to cancer patients who are at increased risk for blood clots. Recently, investigators have noticed that pancreatic, gastric, and colorectal cancer patients who received warfarin survived significantly longer than those taking other anticoagulants.

“Since warfarin has been extensively used in the clinic in cancer patients, we think warfarin could be tested soon as an anticancer drug, particularly for tumours with high levels of VKORC1L1 expression,” Gu said.

The researchers also found that VKORC1L1 is a direct target of p53, a well-known tumour suppressor gene that is mutated in more half of all cancers.

Edited by Diana Spencer, Senior Digital Content Editor, Drug Discovery World

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