Tumorigenesis in neurofibromatosis type 1: role of the microenvironment

Neurofibromatosis Type 1 (NF1) is one of the most common inherited neurological disorders and predisposes patients to develop benign and malignant tumors. Neurofibromas are NF1-associated benign tumors but can cause substantial discomfort and disfigurement. Numerous studies have shown that neurofibromas arise from the Schwann cell lineage but both preclinical mouse models and clinical trials have demonstrated that the neurofibroma tumor microenvironment contributes significantly to tumorigenesis. This offers the opportunity for targeting new therapeutic vulnerabilities to treat neurofibromas. However, a translational gap exists between deciphering the contribution of the neurofibroma tumor microenvironment and clinically applying this knowledge to treat neurofibromas. Here, we discuss the key cellular and molecular components in the neurofibroma tumor microenvironment that can potentially be targeted therapeutically to advance neurofibroma treatment.