Abstract
Abstract
Li-Fraumeni Syndrome (LFS) is caused by germline likely pathogenic/pathogenic variants in the TP53 gene which encodes the p53 tumor suppressor. LFS is a hereditary cancer predisposition syndrome (CPS) with significant lifelong multi-organ cancer risk. As one of the earliest described and less common CPS, knowledge of LFS has grown significantly over time through international collaboration. Future progress in the management of these patients is dependent upon clinical and research advances as facilitated by disease-specific patient/family meetings like the LFS Association bi-annual REACH meeting. This meeting brings together scientists, clinicians, LFS patients and their family members in a collaborative effort to explore challenges in the field. Major current areas of study in LFS include: (1) improving our understanding of specific p53 tumor suppressive functions necessary for cancer development, (2) developing novel classification systems for TP53 variants, (3) exploring more precise genotype-phenotype correlations, (4) defining the cancer spectrum to better inform risk prediction for patients, and (5) understanding the psychosocial implications of an LFS diagnosis. Areas of need were also identified, particularly the need for more precise and practical methods of cancer screening and innovative strategies for targeting the p53 pathway for cancer prevention or early tumor interception. This commentary reflects the major advances in understanding of LFS, including most up-to-date research in the field related to p53 biology, variant interpretation, and clinical care. Herein, we also review areas of late-breaking research and future directions in the field, as a “call to action” for LFS researchers and clinicians.