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（CDKs）在调控细胞周期进程和转录过程中起着关键作用，使其成为癌症研究中的重要靶点。根据调控生物活性的不同，CDKs主要分为两类：转录相关CDKs（如CDK7、8、9、12和13）和细胞周期相关CDKs（如CDK1、2、4和6）。癌症的特征之一就是CDK活性失调，导致细胞分裂失控和肿瘤扩张。近年来研究表明，靶向调控RNA聚合酶II活性及癌细胞生存必需基因表达的转录CDKs，已成为一种有前景的治疗策略。虽然针对转录CDKs选择性抑制剂的研究仍在进行中，但靶向CDK4/6的抑制剂（如帕博西尼和瑞博西尼）已在乳腺癌治疗中展现出令人鼓舞的疗效。CDK7、CDK8和CDK9在结直肠癌、卵巢癌和乳腺癌等多种恶性肿瘤中显示出致癌作用，因此成为极具潜力的治疗靶点。尽管已取得显著进展，开发具有高选择性且脱靶效应可忽略的抑制剂仍面临挑战。本综述通过系统阐述CDKs在癌症生物学中的非转录功能、治疗潜力以及靶向这些激酶面临的困难，强调需要进一步深入研究以优化治疗策略并改善患者预后。
肿瘤(癌症)患者之家