Recent advances in Neurofibromatosis type 1 research: Towards tailored therapeutics and treatment strategies

• 발행기관: 대한의학유전학회
• 저자명: Su Jung Park
• 간행물 정보: 『대한의학유전학회지』제21권 제2호, 51~60쪽, 전체 10쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2024.12.31

국문 초록

Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem disorder caused by germline mutations in the NF1 gene, classified as a RASopathy. The NF1 gene encodes neurofibromin, a RAS GTPase-activating protein that modulates the Ras-MAPK signaling cascade. MEK1 inhibitors targeting the Ras-MAPK pathway were initially developed for cancer treatment and have since expanded their applications to RASopathies due to shared molecular mechanisms. Following the FDA approval of MEK1 inhibitor selumetinib for NF1-associated plexiform neurofibromas, drug development has focused on combination therapies, multi-pathway targeting, AI-driven drug discovery, preclinical models, and orphan drug designation to address a broad spectrum of NF1-associated tumors and conditions. Over the past 30 years, significant progress has been made in understanding NF1. This review aims to summarize recent research advancements that enhance the development of NF1 therapeutics, addressing existing gaps in current knowledge and treatment strategies. Ultimately, this could promote personalized medicine, tailoring treatments to the unique genetic and tumor microenvironmental characteristics of each NF1 patient.

목차

Introduction

FDA-approved Selumetinib and Investigational Mirdametinib: A New Era in NF1-PN Treatment

Genotype-phenotype Correlations in NF1

Mosaic Neurofibromatosis and Loss of Heterozygosity

NF1+/- Tumor Microenvironment

Functional Differences in GAP Activity of NF1 Isoforms: The Role of Exon 23a

Conclusion

Acknowledgements

Funding

References

키워드

Neurofibromatosis 1 GTPase-activating proteins Ras pathway Loss of heterozygosity Tumor microenvironment