Advancing Neurofibromatosis Type 1 Therapies through Basic Research Translation

Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by the growth of both benign and malignant tumors in neural crest cells. Despite extensive research, only one medication has been approved for plexiform neurofibroma treatment, and no specific drugs exist for other associated tumors. Recent studies suggest targeting cellular signaling pathways (Hippo, Janus kinase/signal transducer and activator of transcription, and mitogen-activated protein kinase) and the microenvironment (nerve cells, macrophages, mast cells, and T cells) as potential therapeutic approaches. Several clinical trials are investigating agents that inhibit specific kinases or target signaling molecules in the microenvironment. Despite significant progress, more effective treatments are needed. This paper reviews previous strategies, ongoing clinical trials, and recent advances in basic research related to NF1 and its associated tumor. Data collected from scientific databases and literature highlight the potential of novel therapeutics, including kinase inhibitors, signaling molecule modulators, and microenvironment-targeting drugs. Understanding the underlying mechanisms of tumor development and progression in NF1 is crucial for developing effective therapies. This review provides insights into current strategies, ongoing trials, and recent basic research, aiming to improve treatment outcomes and address unmet needs in NF1 management. By bridging the gap between basic research and clinical translation, this work paves the way for advancing NF1 therapies and bringing novel treatments to patients.