Scientists at the University of Pittsburgh School of Medicine have identified a molecular pathway in liver that can allow an anti-rejection drug to be repurposed for the treatment of certain liver cancers. "Current liver cancer therapies increase the likelihood of survival only by 3 or 4 months, so taking a precision medicine approach to identify the right patient could allow us to repurpose existing drugs to improve treatment success," says Satdarshan Monga, M.D., professor of pathology and founding director of the Pittsburgh Liver Research Center at Pitt's School of Medicine.
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"What we've found is that liver cancers with a specific mutation in the β-catenin gene are possibly more susceptible to rapamycin, a commonly used anti-rejection medication in transplantation," says Monga. "We think this gives us a new precision medicine approach to develop therapies for liver cancer, which often are very resistant to treatment."
These are mouse liver tissues showing cells surrounding the central vein with active mTOR (red) and glutamine synthetase (green) being present in the same cells (yellow).
Credit: Cell Reports/University of Pittsburgh
Investigation of the molecular pathway began with measurements of high levels of a protein called mTOR--a nutrition and energy sensor crucial to cellular metabolism. The protein was present in the same cells where β-catenin was known to be active. This encouraged the researchers to see if the two proteins were functionally linked by creating a mouse model of liver cancer. They added a drug called rapamycin, a known immunosuppressant of mTOR, and found that the tumors decreased in size. This confirmed that mTOR palsy a major role in cancer growth of the liver. "I like to say these tumors are mTOR addicted," said Monga, who is senior author of the study as well as an investigator at the McGowan Institute of Regenerative Medicine and the UPMC Hillman Cancer Center. "Activating mTOR kicks up the protein-making factories in these cells, giving them the resources to divide and grow."
Results of the study were published in Cell Metabolism.
Source: Science Daily