CDK12基因在恶性肿瘤中的研究进展

Research progress of CDK12 gene in malignant tumors

CDK12属于转录相关的细胞周期蛋白依赖性激酶(cyclin-dependent kinases,CDKs),在转录调控、mRNA剪接、DNA损伤修复、细胞生长和分化、调控表观遗传修饰、维持基因组稳定等多种细胞进程中发挥重要作用。目前已在多种实体瘤中检测到CDK12基因的体细胞变异,如前列腺癌、卵巢癌、乳腺癌、黑色素瘤、食管癌、子宫内膜癌、膀胱癌、结直肠癌和头颈鳞状细胞癌等。近期研究表明CDK12发生突变或缺失会引起恶性肿瘤患者对PARP抑制剂、铂类化疗药物以及免疫治疗敏感,因此有望成为肿瘤治疗的新靶点。本文对CDK12的结构、功能及其在恶性肿瘤中的研究进展进行综述,以为临床各类肿瘤的靶向药物研究提供帮助。

CDK12 belongs to the transcription-related cyclin-dependent kinases(CDKs)and plays an important role in various cell processes,including transcriptional regulation,mRNA splicing,DNA damage repair,cell growth and differentiation,regulation of epigenetic modification,and maintenance of genome stability.Somatic CDK12 alterations have been detected in a variety of solid tumors,such as prostate cancer,ovarian cancer,breast cancer,melanoma,esophageal carcinoma,endometrial carcinoma,bladder cancer,colorectal cancer,and head and neck squamous cell carcinoma.Recent studies have shown that CDK12 mutations or deletions can sensitize cancer patients to PARP inhibitors,platinum-based chemotherapy drugs,and immunotherapy.Therefore,CDK12 is expected to be a new molecular target for tumor therapy.In this paper,we review the structure,function and research progress of CDK12 in malignant tumors to facilitate the clinical research of targeted drugs in various tumors.