Neurofibromatosis in the Era of Precision Medicine: Development of MEK Inhibitors and Recent Successes with Selumetinib

Curr Oncol Rep. 2021 Mar 15;23(4):45. doi: 10.1007/s11912-021-01032-y.

Abstract

Purpose of review: Patients with neurofibromatosis type 1 (NF1) are at increased risk for benign and malignant neoplasms. Recently, targeted therapy with the MEK inhibitor class has helped address these needs. We highlight recent successes with selumetinib while acknowledging ongoing challenges for NF1 patients and future directions.

Recent findings: MEK inhibitors have demonstrated efficacy for NF1-related conditions, including plexiform neurofibromas and low-grade gliomas, two common causes of NF1-related morbidity. Active investigations for NF1-related neoplasms have benefited from advanced understanding of the genomic and cell signaling alterations in these conditions and development of sound preclinical animal models. Selumetinib has become the first FDA-approved targeted therapy for NF1 following its demonstrated efficacy for inoperable plexiform neurofibroma. Investigations of combination therapy and the development of a representative NF1 swine model hold promise for translating therapies for other NF1-associated pathology.

Keywords: Combination therapy; Low-grade glioma; MEK inhibitor; Malignant peripheral nerve sheath tumor; Neurofibromatosis; Optic pathway glioma; Plexiform neurofibroma; Selumetinib.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzimidazoles / therapeutic use*
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Neurofibroma, Plexiform / drug therapy
  • Neurofibromatosis 1 / drug therapy*
  • Neurofibromatosis 1 / genetics
  • Precision Medicine
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction
  • Swine

Substances

  • AZD 6244
  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase Kinases