Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Cancer Sci. 2020 Apr;111(4):1058-1064. doi: 10.1111/cas.14355. Epub 2020 Mar 24.
Dysregulation or mutation of DNA binding proteins such as transcription factors (TFs) is associated with the onset and progression of various types of disease, including cancer. Alteration of TF activity occurs in numerous cancer tissues due to gene amplification, deletion, and point mutations, and epigenetic modification. Although cancer-associated TFs are promising targets for cancer therapy, development of drugs targeting these TFs has historically been difficult due to the lack of high-throughput screening methods. Recent advances in technology for identification and selective inhibition of DNA binding proteins enable cancer researchers to develop novel therapeutics targeting cancer-associated TFs. In the present review, we summarize known cancer-associated TFs according to cancer type and introduce recently developed high-throughput approaches to identify selective inhibitors of cancer-associated TFs.
DNA 结合蛋白(如转录因子 [TFs])的失调或突变与各种类型疾病(包括癌症)的发生和进展有关。由于基因扩增、缺失和点突变以及表观遗传修饰,TF 活性在许多癌症组织中发生改变。尽管与癌症相关的 TFs 是癌症治疗的有前途的靶点,但由于缺乏高通量筛选方法,针对这些 TFs 的药物的开发在历史上一直具有挑战性。用于鉴定和选择性抑制 DNA 结合蛋白的技术的最新进展使癌症研究人员能够开发针对与癌症相关的 TFs 的新型治疗方法。在本综述中,我们根据癌症类型总结了已知的与癌症相关的 TFs,并介绍了最近开发的用于鉴定与癌症相关的 TFs 的选择性抑制剂的高通量方法。