Bench-to-Bedside Award Targets Li-Fraumeni Syndrome

Congratulations to Dr. Phillip Dennis from NCI’s Center for Cancer Research, Dr. David Malkin from the University of Toronto, Sharon A. Savage, M.D., Clinical Genetics Branch, and Joseph F. Fraumeni, Jr., M.D., Division Director, who received an NIH Bench-to-Bedside Award for their project “Repositioning metformin as an anti-cancer agent in Li-Fraumeni syndrome.”

Dr. Dennis is leading this multidisciplinary project and will be working with Drs. Malkin, Savage, and Fraumeni to assess the safety and efficacy of metformin as a treatment option for patients with Li-Fraumeni syndrome (LFS), a rare, inherited disorder that predisposes young people to certain cancers, including breast cancer, sarcomas, and a variety of other tumors. LFS is characterized by germline mutations in the p53 tumor suppressor gene, which occur in approximately 70 percent of patients diagnosed with LFS. Previous studies suggest that metformin, which is currently used as an antidiabetic agent, may hold promise as an anticancer agent due to its ability to stimulate the AMP-activated protein kinase pathway, which plays a role in cellular metabolism and regulation. Metformin has also been shown in xenografts to inhibit the growth of p53-deficient tumors. The current study will determine whether metformin can prevent tumor formation or cause tumor regression in animal models of LFS, and it will also investigate the efficacy and safety of metformin through a clinical trial with LFS patients. Currently, few medical options exist for the treatment or prevention of LFS.

The NIH Bench-to-Bedside Award Program fosters collaborations among laboratory, clinical, and population scientists in areas of research that have potential for improving the understanding of an important disease process or for leading investigators to a new therapeutic, preventive, or diagnostic intervention. Projects involving extramural partners are encouraged. The awards are funded with contributions from the Office of Rare Diseases Research, Office of AIDS Research, Office of Research on Women’s Health, the National Center on Minority Health and Health Disparities, the National Center for Research Resources, and matching Institute funds.