{"title":"寻找治疗结节性硬化症的方法:从遗传学到靶向药物治疗。","authors":"Lauren J McEneaney, Andrew R Tee","doi":"10.1016/bs.adgen.2018.11.003","DOIUrl":null,"url":null,"abstract":"<p><p>Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic condition caused by a mutation in either the TSC1 or TSC2 gene. Phenotypically, this leads to aberrant cell growth and the formation of benign tumors called hamartomas in multiple organs. Understanding the mechanisms of pathology that are caused through the presence of disease causing mutations is a real hurdle for many rare genetic disorders; a limiting factor that restricts knowledge of the disease and any hope of a future cure. Through the discovery of the TSC1 and TSC2 genes and the signaling pathways responsible for the pathology of TSC, a new drug target called mechanistic target of rapamycin complex 1 (mTORC1) was discovered. Rapamycin, an mTORC1 inhibitor, is now the only pharmacological therapy approved for the treatment of TSC. This chapter summarizes the success story of TSC and explores the future possibilities of finding a cure.</p>","PeriodicalId":50949,"journal":{"name":"Advances in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.adgen.2018.11.003","citationCount":"19","resultStr":"{\"title\":\"Finding a cure for tuberous sclerosis complex: From genetics through to targeted drug therapies.\",\"authors\":\"Lauren J McEneaney, Andrew R Tee\",\"doi\":\"10.1016/bs.adgen.2018.11.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic condition caused by a mutation in either the TSC1 or TSC2 gene. Phenotypically, this leads to aberrant cell growth and the formation of benign tumors called hamartomas in multiple organs. Understanding the mechanisms of pathology that are caused through the presence of disease causing mutations is a real hurdle for many rare genetic disorders; a limiting factor that restricts knowledge of the disease and any hope of a future cure. Through the discovery of the TSC1 and TSC2 genes and the signaling pathways responsible for the pathology of TSC, a new drug target called mechanistic target of rapamycin complex 1 (mTORC1) was discovered. Rapamycin, an mTORC1 inhibitor, is now the only pharmacological therapy approved for the treatment of TSC. This chapter summarizes the success story of TSC and explores the future possibilities of finding a cure.</p>\",\"PeriodicalId\":50949,\"journal\":{\"name\":\"Advances in Genetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/bs.adgen.2018.11.003\",\"citationCount\":\"19\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/bs.adgen.2018.11.003\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2018/12/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.adgen.2018.11.003","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/12/20 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 19
摘要
结节性硬化症(TSC)是一种罕见的常染色体显性遗传病,由TSC1或TSC2基因突变引起。在表型上,这导致细胞生长异常,并在多个器官中形成称为错构瘤的良性肿瘤。了解由疾病引起的突变引起的病理机制是许多罕见遗传疾病的真正障碍;这是一个限制因素,限制了人们对这种疾病的了解,也限制了未来治愈的希望。通过发现TSC1和TSC2基因及其与TSC病理相关的信号通路,发现了一种新的药物靶点——雷帕霉素复合体1 (mechanistic target of rapamycin complex 1, mTORC1)。雷帕霉素是一种mTORC1抑制剂,是目前唯一被批准用于治疗TSC的药物疗法。本章总结了TSC的成功故事,并探讨了寻找治疗方法的未来可能性。
Finding a cure for tuberous sclerosis complex: From genetics through to targeted drug therapies.
Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic condition caused by a mutation in either the TSC1 or TSC2 gene. Phenotypically, this leads to aberrant cell growth and the formation of benign tumors called hamartomas in multiple organs. Understanding the mechanisms of pathology that are caused through the presence of disease causing mutations is a real hurdle for many rare genetic disorders; a limiting factor that restricts knowledge of the disease and any hope of a future cure. Through the discovery of the TSC1 and TSC2 genes and the signaling pathways responsible for the pathology of TSC, a new drug target called mechanistic target of rapamycin complex 1 (mTORC1) was discovered. Rapamycin, an mTORC1 inhibitor, is now the only pharmacological therapy approved for the treatment of TSC. This chapter summarizes the success story of TSC and explores the future possibilities of finding a cure.
期刊介绍:
Advances in Genetics presents an eclectic mix of articles of use to all human and molecular geneticists. They are written and edited by recognized leaders in the field and make this an essential series of books for anyone in the genetics field.