细胞周期蛋白依赖性激酶抑制剂(CDKIs)的癌症治疗:从实验室到临床。

IF 3.8 3区 生物学 Q1 BIOLOGY
EXCLI Journal Pub Date : 2024-06-04 eCollection Date: 2024-01-01 DOI:10.17179/excli2024-7076
Ali Hassanzadeh, Navid Shomali, Amin Kamrani, Mohammad Sadegh Soltani-Zangbar, Hadi Nasiri, Morteza Akbari
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引用次数: 0

摘要

癌症的一个主要特征是细胞分裂失调,导致细胞异常生长。因此,能够阻止细胞分裂的药物靶点将有助于抗击癌症。细胞增殖的主要调节因子是由细胞周期蛋白和细胞周期蛋白依赖性激酶(CDKs)组成的复合物。美国食品和药物管理局已批准 CDK 抑制剂(CDKIs)用于治疗转移性激素受体阳性乳腺癌。具体来说,CDK4/6 CDKIs 可阻断 CDK4 和 CDK6 的酶活性。遗憾的是,大多数第一代 CDK 抑制剂(又称泛 CDK 抑制剂,因为它们针对多个 CDK)由于副作用严重和缺乏选择性而未被授权用于临床。与此相反,目前已经取得了重大进展,允许在治疗中使用泛 CDK 抑制剂。值得注意的是,近年来由于联合治疗策略的出现,泛 CDK 抑制剂的毒性和负面影响已有所减轻。因此,在联合治疗方案中使用泛 CDK 抑制剂时,临床应用前景一片光明。本综述回顾了 CDK 家族的成员及其在细胞周期调控中的主要作用。接下来,我们概述了 CDK 抑制剂的研究现状。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cancer therapy by cyclin-dependent kinase inhibitors (CDKIs): bench to bedside.

A major characteristic of cancer is dysregulated cell division, which results in aberrant growth of cells. Consequently, medicinal targets that prevent cell division would be useful in the fight against cancer. The primary regulator of proliferation is a complex consisting of cyclin and cyclin-dependent kinases (CDKs). The FDA has granted approval for CDK inhibitors (CDKIs) to treat metastatic hormone receptor-positive breast cancer. Specifically, CDK4/6 CDKIs block the enzyme activity of CDK4 and CDK6. Unfortunately, the majority of first-generation CDK inhibitors, also known as pan-CDK inhibitors because they target multiple CDKs, have not been authorized for clinical use owing to their serious side effects and lack of selection. In contrast to this, significant advancements have been created to permit the use of pan-CDK inhibitors in therapeutic settings. Notably, the toxicity and negative consequences of pan-CDK inhibitors have been lessened in recent years thanks to the emergence of combination therapy tactics. Therefore, pan-CDK inhibitors have renewed promise for clinical use when used in a combination regimen. The members of the CDK family have been reviewed and their primary roles in cell cycle regulation were covered in this review. Next, we provided an overview of the state of studies on CDK inhibitors.

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来源期刊
EXCLI Journal
EXCLI Journal BIOLOGY-
CiteScore
8.00
自引率
2.20%
发文量
65
审稿时长
6-12 weeks
期刊介绍: EXCLI Journal publishes original research reports, authoritative reviews and case reports of experimental and clinical sciences. The journal is particularly keen to keep a broad view of science and technology, and therefore welcomes papers which bridge disciplines and may not suit the narrow specialism of other journals. Although the general emphasis is on biological sciences, studies from the following fields are explicitly encouraged (alphabetical order): aging research, behavioral sciences, biochemistry, cell biology, chemistry including analytical chemistry, clinical and preclinical studies, drug development, environmental health, ergonomics, forensic medicine, genetics, hepatology and gastroenterology, immunology, neurosciences, occupational medicine, oncology and cancer research, pharmacology, proteomics, psychiatric research, psychology, systems biology, toxicology
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