Division of Cancer and Genetics, Cardiff University, Cardiff, United Kingdom.
Division of Cancer and Genetics, Cardiff University, Cardiff, United Kingdom.
Adv Genet. 2019;103:91-118. doi: 10.1016/bs.adgen.2018.11.003. Epub 2018 Dec 20.
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.
结节性硬化症(TSC)是一种罕见的常染色体显性遗传疾病,由 TSC1 或 TSC2 基因突变引起。表型上,这会导致异常细胞生长和良性肿瘤的形成,称为错构瘤,发生在多个器官中。了解导致疾病突变的病理机制对于许多罕见遗传疾病来说是一个真正的障碍;这是一个限制因素,限制了对疾病的认识和任何未来治愈的希望。通过发现 TSC1 和 TSC2 基因以及负责 TSC 病理的信号通路,发现了一种名为雷帕霉素复合物 1(mTORC1)的新药物靶点。雷帕霉素是一种 mTORC1 抑制剂,现在是唯一被批准用于治疗 TSC 的药理学疗法。本章总结了 TSC 的成功故事,并探讨了寻找治愈方法的未来可能性。