Targeting the MYCN-MDM2 pathways for cancer therapy:Are they druggable?  

作　　者：Wei Wang Yi Du Sayantap Datta Josef F.Fowler Hannah T.Sang Najah Aibadari Wei Li Jennifer Foster Ruiwen Zhang 

机构地区：[1]Department of Pharmacological and Pharmaceutical Sciences,College of Pharmacy,University of Houston,Houston,TX 77204,USA [2]Drug Discovery Institute,University of Houston,Houston,TX 77204,USA [3]College of Pharmacy,The University of Tennessee Health Science Center,Memphis,TN 38163,USA [4]Texas Children's Hospital,Department of Pediatrics,Section of Hematology-Oncology Baylor College of Medicine,Houston,TX 77030,USA

出　　处：《Genes & Diseases》2025年第2期271-287,共17页基因与疾病(英文)

基　　金：supported by the National Institutes of Health (NIH)/National Cancer Institute (No.R01CA214019 to RZ);support was provided by the NCl grant R01CA240447 to WL.

摘　　要：Targeting oncogenes and their interactive partners is an effective approach to developing novel targeted therapies for cancer and other chronic diseases.We and others have long suggested the MDM2 oncogene being an excellent target for cancer therapy,based on its p53-dependent and-independent oncogenic activities in a variety of cancers.The MYC family proteins are transcription factors that also regulate diverse biological functions.Dysregulation of MYC,such as amplification of MYCN,is associated with tumorigenesis,especially for neuro-blastoma.Although the general survival rate of neuroblastoma patients has significantly improved over the past few decades,high-risk neuroblastoma still presents a poor prognosis.Therefore,innovative and more potent therapeutic strategies are needed to eradicate these aggressive neoplasms.This review focuses on the oncogenic properties of MYCN and its molecular regulation and summarizes the major therapeutic strategies being developed based on pre-clinical findings.We also highlight the potential benefits of targeting both the MYCN and MDM2 oncogenes,providing preclinical evidence of the efficacy and safety of this approach.In conclusion,the development of effective small molecules that inhibit both MYCN and MDM2 represents a promising new strategy for the treatment of neuroblastoma and other cancers.

关 键 词：MDM2 MYCN NEUROBLASTOMA Signaling pathway Targeted therapy 

分 类 号：R73[医药卫生—肿瘤]