Pub Date : 2023-10-01DOI: 10.1016/j.gendis.2023.101156
Wei Wang, Yi Du, Sayantap Datta, Josef F. Fowler, Hannah T. Sang, Najah Ghazi Albadari, Wei Li, Jennifer Foster, Ruiwen Zhang
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 neuroblastoma. 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 preclinical 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.
{"title":"Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?","authors":"Wei Wang, Yi Du, Sayantap Datta, Josef F. Fowler, Hannah T. Sang, Najah Ghazi Albadari, Wei Li, Jennifer Foster, Ruiwen Zhang","doi":"10.1016/j.gendis.2023.101156","DOIUrl":"https://doi.org/10.1016/j.gendis.2023.101156","url":null,"abstract":"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 neuroblastoma. 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 preclinical 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.","PeriodicalId":37979,"journal":{"name":"Genes and Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136094720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-18DOI: 10.1016/j.gendis.2020.06.002
Li Mu, Xiaobing Deng, Ke Wu, Chao Yang
{"title":"LncRNA KCNQ1OT1 promotes cisplatin resistance of osteosarcoma cancer cells through the miR-335-5p/β-catenin axis","authors":"Li Mu, Xiaobing Deng, Ke Wu, Chao Yang","doi":"10.1016/j.gendis.2020.06.002","DOIUrl":"https://doi.org/10.1016/j.gendis.2020.06.002","url":null,"abstract":"","PeriodicalId":37979,"journal":{"name":"Genes and Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.gendis.2020.06.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47149116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-03-01DOI: 10.1016/J.GENDIS.2017.02.002
Yuting Ma, X. Tong, Yong-de Liao
{"title":"The metabolic switch of cancer : From the 2016 Sino-US Symposium on Cancer Metabolism, Chongqing, P.R. China, October 10–11, 2016","authors":"Yuting Ma, X. Tong, Yong-de Liao","doi":"10.1016/J.GENDIS.2017.02.002","DOIUrl":"https://doi.org/10.1016/J.GENDIS.2017.02.002","url":null,"abstract":"","PeriodicalId":37979,"journal":{"name":"Genes and Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.GENDIS.2017.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44015064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-08-18DOI: 10.1016/J.GENDIS.2015.08.002
Yujie Lai, F. Sun, Guo-Jun Chen
{"title":"WITHDRAWN: Adult neurogenesis: Is it showtime for clinical translation?","authors":"Yujie Lai, F. Sun, Guo-Jun Chen","doi":"10.1016/J.GENDIS.2015.08.002","DOIUrl":"https://doi.org/10.1016/J.GENDIS.2015.08.002","url":null,"abstract":"","PeriodicalId":37979,"journal":{"name":"Genes and Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/J.GENDIS.2015.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54441236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}