CtBP- an emerging oncogene and novel small molecule drug target: Advances in the understanding of its oncogenic action and identification of therapeutic inhibitors.
CtBP- an emerging oncogene and novel small molecule drug target: Advances in the understanding of its oncogenic action and identification of therapeutic inhibitors.
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DOI：
10.1080/15384047.2017.1323586
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发表时间：
2017-06-03
影响因子：
3.6
通讯作者：
Grossman SR
中科院分区：
文献类型：
--
作者：
Dcona MM;Morris BL;Ellis KC;Grossman SR
C-末端结合蛋白（CtBP）1和2是在许多癌症类型中过表达的致癌转录辅助调节因子，其表达水平与更差的预后结果和侵袭性肿瘤特征相关。CtBP负调节许多肿瘤抑制基因的表达，同时共激活促进增殖、上皮-间质转化和癌症干细胞自我更新活性的基因。鉴于这一证据，开发减轻CtBP功能的新型抑制剂可能会提供临床可行的治疗工具。本文综述了近年来在理解CtBP结构、在肿瘤进展中的作用以及针对CtBP脱氢酶活性和其他功能的CtBP抑制剂的发现和开发方面取得的进展，重点介绍了当前抑制剂设计背后的理论和原理。我们提供了对合理联合治疗的未来开发和使用的见解，这些治疗可能进一步增强CtBP抑制剂的疗效，特别是针对肿瘤内的转移和癌症干细胞群体。
C-terminal Binding Proteins (CtBP) 1 and 2 are oncogenic transcriptional co-regulators overexpressed in many cancer types, with their expression level correlating to worse prognostic outcomes and aggressive tumor features. CtBP negatively regulates the expression of many tumor suppressor genes, while coactivating genes that promote proliferation, epithelial-mesenchymal transition, and cancer stem cell self-renewal activity. In light of this evidence, the development of novel inhibitors that mitigate CtBP function may provide clinically actionable therapeutic tools. This review article focuses on the progress made in understanding CtBP structure, role in tumor progression, and discovery and development of CtBP inhibitors that target CtBP's dehydrogenase activity and other functions, with a focus on the theory and rationale behind the designs of current inhibitors. We provide insight into the future development and use of rational combination therapy that may further augment the efficacy of CtBP inhibitors, specifically addressing metastasis and cancer stem cell populations within tumors.
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影响因子：
8.4
作者：
Birts CN;Nijjar SK;Mardle CA;Hoakwie F;Duriez PJ;Blaydes JP;Tavassoli A
通讯作者：
Tavassoli A
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作者：
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通讯作者：
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作者：
Bergman LM;Morris L;Darley M;Mirnezami AH;Gunatilake SC;Blaydes JP
通讯作者：
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