Cyclin-dependent kinases (CDKs) are key regulators of both cell cycle progression and transcription. Since dysregulation of CDKs is a frequently occurring event driving tumorigenesis, CDKs have been tested extensively as targets for cancer therapy. Cyclin-dependent kinase 12 (CDK12) is a transcription-associated kinase which participates in various cellular processes, including DNA damage response, development and cellular differentiation, as well as splicing and pre-mRNA processing. CDK12 mutations and amplification have been recently reported in different types of malignancies, including loss-of-function mutations in high-grade serous ovarian carcinomas, and that has led to assumption that CDK12 is a tumor suppressor. On the contrary, CDK12 overexpression in other tumors suggests the possibility that CDK12 has oncogenic properties, similarly to other transcription-associated kinases. In this review, we discuss current knowledge concerning the role of CDK12 in ovarian and breast tumorigenesis and the potential for chemical inhibitors of CDK12 in future cancer treatment.

中文翻译：

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CDK12在肿瘤发生中的新兴作用。

细胞周期蛋白依赖性激酶（CDK）是细胞周期进程和转录的关键调节因子。由于CDK的失调是驱动肿瘤发生的一个经常发生的事件，因此CDK已作为癌症治疗的靶标进行了广泛的测试。细胞周期蛋白依赖性激酶12（CDK12）是一种转录相关激酶，它参与各种细胞过程，包括DNA损伤应答，发育和细胞分化以及剪接和前mRNA加工。最近已经在不同类型的恶性肿瘤中报道了CDK12突变和扩增，包括高度浆液性卵巢癌中的功能丧失突变，这导致人们认为CDK12是一种肿瘤抑制因子。相反，CDK12在其他肿瘤中的过度表达表明CDK12具有致癌特性，与其他转录相关激酶类似。在这篇综述中，我们讨论了有关CDK12在卵巢和乳腺肿瘤发生中的作用以及CDK12化学抑制剂在未来癌症治疗中的潜力的当前知识。