Department of Oncology, Montefiore Einstein, Bronx, NY, USA; Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, USA.
Department of Oncology, Montefiore Einstein, Bronx, NY, USA; Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, USA; Department of Molecular Pharmacology, Montefiore Einstein, Bronx, NY, USA.
Biochem Pharmacol. 2024 Nov;229:116470. doi: 10.1016/j.bcp.2024.116470. Epub 2024 Aug 8.
Cyclin-dependent kinase 9 (CDK9) regulates mRNA transcription by promoting RNA Pol II elongation. CDK9 is now emerging as a potential therapeutic target for cancer, since its overexpression has been found to correlate with cancer development and worse clinical outcomes. While much work on CDK9 inhibition has focused on hematologic malignancies, the role of this cancer driver in solid tumors is starting to come into focus. Many solid cancers also overexpress CDK9 and depend on its activity to promote downstream oncogenic signaling pathways. In this review, we summarize the latest knowledge of CDK9 biology in solid tumors and the studies of small molecule CDK9 inhibitors. We discuss the results of the latest clinical trials of CDK9 inhibitors in solid tumors, with a focus on key issues to consider for improving the therapeutic impact of this drug class.
细胞周期蛋白依赖性激酶 9（CDK9）通过促进 RNA 聚合酶 II 延伸来调节 mRNA 转录。由于 CDK9 的过度表达与癌症的发展和更差的临床结果相关，因此它现在作为癌症的潜在治疗靶点而受到关注。虽然 CDK9 抑制的许多研究都集中在血液恶性肿瘤上，但这种癌症驱动因子在实体肿瘤中的作用开始成为焦点。许多实体瘤也过度表达 CDK9，并依赖其活性来促进下游致癌信号通路。在这篇综述中，我们总结了 CDK9 在实体肿瘤中的生物学特性以及小分子 CDK9 抑制剂的研究最新进展。我们讨论了 CDK9 抑制剂在实体肿瘤中的最新临床试验结果，重点讨论了为提高此类药物的治疗效果而需要考虑的关键问题。
