Neurofibromin in Breast Cancer

Breast cancer is one of the most common lethal malignancies in women. Identifying new molecular vulnerabilities to develop clinically actionable biomarkers and targeted treatments to improve patient outcomes is crucial in this disease. In recent years, neurofibromin (NF1), encoded by the neurofibromin 1 gene (NF1), whose germline genetic variations are known to lead to a tumor-predisposition disease, neurofibromatosis type 1, has emerged as an important determinant of breast cancer etiology and pathogenesis, not only in this rare hereditary condition but also in sporadic breast cancer. NF1 is a tumor suppressor and an upstream negative regulator of the oncogenic Ras signaling pathway. Genetic variations in NF1 and/or downregulation of its expression, commonly observed in sporadic breast cancer, are associated with increased cancer cell proliferation, growth, migration, invasion, deregulation of local anti-cancer immune responses, and aggressive phenotypes. Clinically, downregulation of NF1 function correlates with worse patient survival outcomes and is implicated in resistance to breast cancer treatments, particularly anti-hormonal therapies. Various therapeutic strategies have been developed and studied for targeting NF1 and its associated pathways. Combined, these data indicate that NF1 represents a promising molecular vulnerability and clinically actionable target in breast cancer.