Treatment of neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a genetic multisystemic disorder involving the skin, the central and peripheral nervous systems, bones, and the cardiovascular and endocrine systems. This condition is caused by inherited or de novo mutations of the NF1 gene at the 17q11.2 chromosomal region, a gene that codes for the protein neurofibromin. Neurofibromin is particularly expressed in neural cells and inhibits the RAS pathway, which regulates cellular proliferation and differentiation. The typically age-dependent emergence of diagnostic signs and the risk for severe complications in the first years of life simultaneously makes a precocious diagnosis crucial and makes the management of children with suspected NF1 challenging. Currently, no standardized specific treatments for NF1 and its complications are available. However, in recent years, increasing knowledge of the pathogenetic mechanisms has motivated the scientific search behind targeted biological agents that might change the course of the disease. Numerous clinical trials for the treatment of the most typical NF1 complications, such as plexiform neurofibromas (Ns) and NF1-related tumors, have been conducted. Consequently, encouraging in vitro and in vivo results are emerging. Insufficient efficacy and safety in in vivo data do not permit the routine use of these drugs in clinical practice. Radiotherapy appears to be indicated only for high-grade soft-tissue sarcomas, whereas surgical approaches should be considered for malignant peripheral nerve sheath tumors (MPNSTs) and Ns, optic pathway gliomas, and bone dystrophic changes because they might improve quality of life. Further prospective studies, however, are needed to confirm the efficacy, safety, and cost/benefit ratio of new therapeutic approaches and the optimal timing for their use in patients with NF1.