Shen Shen, Dean Dylan C, Yu Zujiang, Duan Zhenfeng
Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Sarcoma Biology Laboratory, Department of Orthopedic Surgery, David Geffen School of Medicine at University of Los Angeles, Los Angeles, CA, USA.
Hepatol Res. 2019 Oct;49(10):1097-1108. doi: 10.1111/hepr.13353. Epub 2019 May 26.
Liver cancer is the fourth leading cause of cancer related mortality in the world, with hepatocellular carcinoma (HCC) representing the most common primary subtype. Two-thirds of HCC patients have advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. The development of novel and more effective agents is required. Cyclin-dependent kinases (CDKs) constitute a family of 21 different protein kinases involved in regulating cell proliferation, apoptosis, and drug resistance, and are evaluated in preclinical and clinical trials as chemotherapeutics. To summarize and discuss the therapeutic potential of targeting CDKs in HCC, recent published articles identified from PubMed were comprehensively reviewed. The key words included hepatocellular carcinoma, cyclin-dependent kinases, and CDK inhibitors. This review focuses on the emerging evidence from studies describing the genetic and functional aspects of CDKs in HCC. We also present an overview of CDK inhibitors that have shown efficacy in laboratory studies of HCC. Although many of the studies assessing CDK-targeting therapies in HCC are at the preclinical stage, there is significant evidence that CDK inhibitors used alone or in combination with established chemotherapy drugs could have significant applications in HCC.
肝癌是全球癌症相关死亡的第四大主要原因，其中肝细胞癌（HCC）是最常见的原发性亚型。三分之二的HCC患者在确诊时已处于疾病晚期，对于这些患者，治疗策略仍然有限。此外，按照目前的治疗方案，手术切除后肿瘤复发率很高。因此需要开发新型且更有效的药物。细胞周期蛋白依赖性激酶（CDK）由21种不同的蛋白激酶组成，参与调节细胞增殖、凋亡和耐药性，并作为化学治疗药物在临床前和临床试验中进行评估。为了总结和讨论靶向CDK在HCC中的治疗潜力，我们全面回顾了从PubMed中检索到的近期发表的文章。关键词包括肝细胞癌、细胞周期蛋白依赖性激酶和CDK抑制剂。本综述重点关注描述HCC中CDK的遗传和功能方面的研究中出现的证据。我们还概述了在HCC实验室研究中已显示出疗效的CDK抑制剂。尽管许多评估HCC中靶向CDK治疗的研究仍处于临床前阶段，但有大量证据表明，单独使用CDK抑制剂或与既定的化疗药物联合使用，可能在HCC中具有重要应用价值。
