Alrouji Mohammed, Alshammari Mohammed S, Anwar Saleha, Venkatesan Kumar, Shamsi Anas
Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia.
Cancers (Basel). 2025 May 3;17(9):1554. doi: 10.3390/cancers17091554.
Cyclin-dependent kinases (CDKs) are pivotal in regulating cell cycle progression and transcription, making them crucial targets in cancer research. The two types of CDKs that regulate different biological activities are transcription-associated CDKs (e.g., CDK7, 8, 9, 12, and 13) and cell cycle-associated CDKs (e.g., CDK1, 2, 4, and 6). One characteristic of cancer is the dysregulation of CDK activity, which results in unchecked cell division and tumor expansion. Targeting transcriptional CDKs, which control RNA polymerase II activity and gene expression essential for cancer cell survival, has shown promise as a therapeutic approach in recent research. While research into selective inhibitors for transcriptional CDKs is ongoing, inhibitors that target CDK4/6, such as palbociclib and ribociclib, have demonstrated encouraging outcomes in treating breast cancer. CDK7, CDK8, and CDK9 are desirable targets for therapy since they have shown oncogenic roles in a variety of cancer types, such as colorectal, ovarian, and breast malignancies. Even with significant advancements, creating selective inhibitors with negligible off-target effects is still difficult. This review highlights the need for more research to optimize therapeutic strategies and improve patient outcomes by giving a thorough overview of the non-transcriptional roles of CDKs in cancer biology, their therapeutic potential, and the difficulties in targeting these kinases for cancer treatment.
细胞周期蛋白依赖性激酶（CDK）在调节细胞周期进程和转录中起关键作用，使其成为癌症研究中的重要靶点。调节不同生物学活性的两类CDK分别是与转录相关的CDK（如CDK7、8、9、12和13）和与细胞周期相关的CDK（如CDK1、2、4和6）。癌症的一个特征是CDK活性失调，这会导致细胞不受控制地分裂和肿瘤扩张。靶向控制RNA聚合酶II活性和癌细胞存活所必需的基因表达的转录CDK，在最近的研究中已显示出作为一种治疗方法的前景。虽然针对转录CDK的选择性抑制剂的研究正在进行中，但靶向CDK4/6的抑制剂，如帕博西尼和瑞博西尼，在治疗乳腺癌方面已显示出令人鼓舞的结果。CDK7、CDK8和CDK9是理想的治疗靶点，因为它们在多种癌症类型中，如结直肠癌、卵巢癌和乳腺癌中，已显示出致癌作用。即使取得了重大进展，开发具有可忽略不计的脱靶效应的选择性抑制剂仍然很困难。本综述通过全面概述CDK在癌症生物学中的非转录作用、它们的治疗潜力以及针对这些激酶进行癌症治疗的困难，强调了需要更多研究来优化治疗策略并改善患者预后。
