Robert Galvin1, Adrienne L Watson2, David A Largaespada3, Nancy Ratner4, Sara Osum3, Christopher L Moertel5,6. 1. Divisions of Pediatric Hematology & Oncology and Bone Marrow Transplant, University of Minnesota, Minneapolis, MN, USA. 2. Recombinetics, Inc., Saint Paul, MN, USA. 3. Division of Pediatric Hematology & Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. 4. Cincinnati Children's Hospital Division of Exp. Hematology and Cancer Biology, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA. 5. Division of Pediatric Hematology & Oncology, University of Minnesota, Minneapolis, MN, USA. moert001@umn.edu. 6. Pediatric Hematology MMC 484 Mayo, 8484B (Campus Delivery Code), 420 Delaware St SE, Minneapolis, MN, 55455, USA. moert001@umn.edu.
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.
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.
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