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细胞周期蛋白依赖性激酶4(CDK4)在胰腺癌发病机制中的作用。

The Role of CDK4 in the Pathogenesis of Pancreatic Cancer.

作者信息

Jiggens Emily, Mortoglou Maria, Grant Guy H, Uysal-Onganer Pinar

机构信息

Cancer Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK.

Department of Life Sciences, University of Bedfordshire, Park Square, Luton LU1 3JU, UK.

出版信息

Healthcare (Basel). 2021 Oct 30;9(11):1478. doi: 10.3390/healthcare9111478.

Abstract

Pancreatic cancer (PC) continues to have the lowest overall survival and the lack of effective early diagnosis. Cyclin-dependent kinase 4 (CDK4) plays a fundamental role in the orderly progression of the cell cycle, binding to cyclin D to promote the progression through the G1/2 transition. The inhibition of CDK4/6 has therefore gained substantial interest in the hope of new and effective therapeutics in multiple cancers, such as advanced metastatic breast cancer. While the use of these agents is encouraging, their potential is yet to be fully explored. In this study we used the GLOBOCAN database to understand the most recent epidemiology of PC, Human Protein Atlas and KEGG to highlight the role, prevalence, and significance on patient survival of CDK4 in PC. We found that CDK4 cannot be used as prognostic in PC and no significant differences were observed between CDK4 expression and the patient's clinical status, though larger studies, especially concerning CDK4 protein expressions, are required for a more thorough understanding. The use of CDK4/6 inhibitors in PC is still in clinical trials. However, due to only modest improvements observed in the use of single-agent therapies, efforts have focused on combinatorial approaches.

摘要

胰腺癌(PC)的总体生存率仍然是所有癌症中最低的,且缺乏有效的早期诊断方法。细胞周期蛋白依赖性激酶4(CDK4)在细胞周期的有序进程中发挥着重要作用,它与细胞周期蛋白D结合,促进细胞通过G1/S期转换。因此,抑制CDK4/6在多种癌症(如晚期转移性乳腺癌)中有望成为新的有效治疗方法,受到了广泛关注。虽然这些药物的应用前景令人鼓舞,但其潜力尚未得到充分探索。在本研究中,我们使用了全球癌症发病率数据库(GLOBOCAN)来了解PC的最新流行病学情况,利用人类蛋白质图谱(Human Protein Atlas)和京都基因与基因组百科全书(KEGG)来突出CDK4在PC中的作用、患病率及其对患者生存的意义。我们发现,CDK4不能作为PC的预后指标,且CDK4表达与患者临床状态之间未观察到显著差异,不过需要开展更大规模的研究,尤其是关于CDK4蛋白表达的研究,以便更全面地了解情况。CDK4/6抑制剂在PC治疗中的应用仍处于临床试验阶段。然而,由于单药治疗仅观察到适度改善,目前的研究重点已转向联合治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/765d/8620733/5c356edabe04/healthcare-09-01478-g001.jpg

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