Therapeutic targets for malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft-tissue sarcomas with dismal prognosis. Complete resection, which is the only known definitive therapy, is not feasible with every tumor, and local recurrence after surgery is another challenge to successful treatment. Treatments used with other sarcoma types have not proven beneficial to MPNST patients. Targeted therapies blocking several signaling pathways known to drive MPNST pathogenesis have also not improved patient outcomes in clinical trials. This review discusses existing therapies and targeted chemotherapeutic options currently being tested clinically, and potential therapeutic avenues identified in preclinical studies that include targeting signaling pathways such as the HIPPO-YAP pathway and epigenetic mechanisms as well as multi-agent strategies.