< em > NF1 < /em > alterations in cancers: therapeutic implications in precision medicine

Expert Opin Investig Drugs. 2023 Sep 25. doi: 10.1080/13543784.2023.2263836. Online ahead of print.ABSTRACTINTRODUCTION: NF1 is a tumor suppressor gene encoding neurofibromin, an inhibitor of the RAS/MAPK and PI3K-AKT-mTOR signaling pathways. NF1 germline pathogenic variants cause the tumor predisposition syndrome neurofibromatosis type 1. Targeted therapies (MEK inhibitors) have been approved for benign nerve sheath tumors in neurofibromatosis type 1 patients. NF1 somatic alterations are present in ~ 5% of all human sporadic cancers. In melanomas, acute myeloid leukemias and lung adenocarcinomas, the NF1 somatic alteration frequency is higher (~15%). However, to date, the therapeutic impact of NF1 somatic alterations is poorly investigated.AREAS COVERED: This review presents a comprehensive overview of targeted therapies and immunotherapies currently developed and evaluated in vitro and in vivo for NF1-altered cancer treatment. A PubMed database literature review was performed to select relevant original articles. Active clinical trials were researched in ClinicalTrials.gov database in August 2022. TCGA and HGMD® databases were consulted.EXPERT OPINION: This review highlights the need to better understand the molecular mechanisms of NF1-altered tumors and the development of innovative strategies to effectively target NF1-loss in human cancers. One of the current major challenges in cancer management is the targeting of tumor suppressor genes such as NF1 gene. Currently, mos...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Authors: Source Type: research