Mitra Partha
Pre-clinical Division, Vaxxas Pty. Ltd. Translational Research Institute, Woolloongabba QLD 4102, Australia.
Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Woolloongabba QLD 4102, Australia.
Ann Transl Med. 2018 Nov;6(22):443. doi: 10.21037/atm.2018.09.62.
Basal transcription factors have never been considered as a priority target in the field of drug discovery. However, their unparalleled roles in decoding the genetic information in response to the appropriate signal and their association with the disease progression are very well-established phenomena. Instead of considering transcription factors as such a target, in this review, we discuss about the potential of the regulatory mechanisms that control their gene expression. Based on our recent understanding about the critical roles of at the cellular and molecular level in several types of cancers, we discuss here how MLL-fusion protein centred SEC in leukaemia, ligand-estrogen receptor (ER) complex in breast cancer (BC) and NF-κB and associated factors in colorectal cancer regulate the transcription of this gene. We further discuss plausible strategies, specific to each cancer type, to target those bona fide activators/co-activators, which control the regulation of this gene and therefore to shed fresh light in targeting the transcriptional regulation as a novel approach to the future drug discovery in cancer.
基础转录因子在药物研发领域从未被视为优先靶点。然而,它们在响应适当信号时解码遗传信息方面所发挥的无与伦比的作用以及它们与疾病进展的关联,都是已被充分证实的现象。在本综述中,我们并未将转录因子视为这样一个靶点,而是讨论控制其基因表达的调控机制的潜力。基于我们最近对几种癌症在细胞和分子水平上的关键作用的理解,我们在此讨论白血病中以MLL融合蛋白为中心的SEC、乳腺癌(BC)中的配体 - 雌激素受体(ER)复合物以及结直肠癌中的NF - κB和相关因子如何调节该基因的转录。我们进一步讨论针对每种癌症类型的合理策略,以靶向那些真正的激活剂/共激活剂,这些激活剂/共激活剂控制该基因的调控,从而为将转录调控作为癌症未来药物研发的一种新方法提供新的思路。