Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne 8006, Victoria, Australia.
Nat Rev Cancer. 2013 May;13(5):299-314. doi: 10.1038/nrc3496.
Mutations that directly affect transcription by RNA polymerases rank among the most central mediators of malignant transformation, but the frequency of new anticancer drugs that selectively target defective transcription apparatus entering the clinic has been limited. This is because targeting the large protein-protein and protein-DNA interfaces that control both generic and selective aspects of RNA polymerase transcription has proved extremely difficult. However, recent technological advances have led to a 'quantum leap' in our comprehension of the structure and function of the core RNA polymerase components, how they are dysregulated in a broad range of cancers and how they may be targeted for 'transcription therapy'.
直接影响 RNA 聚合酶转录的突变是恶性转化的最主要调节因子之一,但能选择性靶向缺陷转录装置的新型抗癌药物进入临床的频率有限。这是因为靶向控制 RNA 聚合酶转录的通用和选择性方面的大型蛋白质-蛋白质和蛋白质-DNA 界面极具挑战性。然而,最近的技术进步使我们对核心 RNA 聚合酶成分的结构和功能、它们在广泛的癌症中失调的方式以及它们如何被靶向用于“转录治疗”有了“质的飞跃”的理解。