Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease caused by inherited or de novo germline pathogenic variants in TP53. Individuals with LFS have a 70–100% lifetime risk of developing cancer. The current standard of care involves annual surveillance with whole-body and brain MRI (WB-MRI) and clinical review; however, there are no chemoprevention agents licensed for individuals with LFS. Preclinical studies in LFS murine models show that the anti-diabetic drug metformin is chemopreventive and, in a pilot intervention trial, short-term use of metformin was well-tolerated in adults with LFS. However, metformin’s mechanism of anticancer activity in this context is unclear..
(gebruik vertalen voor Nederlands)