Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94158, USA.
Nat Rev Drug Discov. 2012 Oct;11(10):790-811. doi: 10.1038/nrd3810. Epub 2012 Sep 24.
Many drugs that target transforming growth factor-β (TGFβ) signalling have been developed, some of which have reached Phase III clinical trials for a number of disease applications. Preclinical and clinical studies indicate the utility of these agents in fibrosis and oncology, particularly in augmentation of existing cancer therapies, such as radiation and chemotherapy, as well as in tumour vaccines. There are also reports of specialized applications, such as the reduction of vascular symptoms of Marfan syndrome. Here, we consider why the TGFβ signalling pathway is a drug target, the potential clinical applications of TGFβ inhibition, the issues arising with anti-TGFβ therapy and how these might be tackled using personalized approaches to dosing, monitoring of biomarkers as well as brief and/or localized drug-dosing regimens.
许多针对转化生长因子-β（TGFβ）信号的药物已经被开发出来，其中一些已经进入了针对多种疾病应用的 III 期临床试验。临床前和临床研究表明，这些药物在纤维化和肿瘤学方面具有实用性，特别是在增强现有的癌症治疗方法方面，如放疗和化疗，以及肿瘤疫苗方面。也有一些关于专门应用的报道，如减少马凡综合征的血管症状。在这里，我们考虑为什么 TGFβ 信号通路是一个药物靶点，TGFβ 抑制的潜在临床应用，抗 TGFβ 治疗中出现的问题，以及如何使用个性化的剂量、生物标志物监测以及短暂和/或局部药物剂量方案来解决这些问题。
