Inhibiting the Priming for Cancer in Li-Fraumeni Syndrome

SIMPLE SUMMARY: Li-Fraumeni Syndrome (LFS) is a rare cancer pre-disposition syndrome associated with a germline mutation in the TP53 tumour suppressor gene. People with LFS have a 90% chance of suffering one or more cancers in their lifetime. No treatments exist to reduce this cancer risk. This paper reviews the evidence for how cancers start in people with LFS and proposes that a series of commonly used non-cancer drugs, including metformin and aspirin, can help reduce that lifetime risk of cancer. ABSTRACT: The concept of the pre-cancerous niche applies the ‘seed and soil’ theory of metastasis to the initial process of carcinogenesis. TP53 is at the nexus of this process and, in the context of Li-Fraumeni Syndrome (LFS), is a key determinant of the conditions in which cancers are formed and progress. Important factors in the creation of the pre-cancerous niche include disrupted tissue homeostasis, cellular metabolism and chronic inflammation. While druggability of TP53 remains a challenge, there is evidence that drug re-purposing may be able to address aspects of pre-cancerous niche formation and thereby reduce the risk of cancer in individuals with LFS.