PARP抑制剂在肿瘤治疗中的最新进展

Q4 Pharmacology, Toxicology and Pharmaceutics
Pulla Prudvi Raj, Kaviarasan L, Gowramma B, Kalirajan R, Praveen T.K, Divya jyothi Palati
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引用次数: 1

摘要

聚[adp -核糖]聚合酶-1 [PARP-1]是一种染色质结合的核酶,在DNA损伤时被激活,它通过结合DNA断裂并吸引DNA修复蛋白到损伤部位来促进DNA修复。在黑色素瘤、乳腺癌、肺癌和其他肿瘤疾病中观察到PARP-1表达升高。PARP-1直接或间接地与多种致癌蛋白相互作用,并调节多种转录因子,从而调节癌变。有大量的临床前和临床数据支持PARP-1抑制剂[PARP-1i]在表达同源重组缺陷的癌症中使用,如BRCA-1/2基因突变。因此,治疗性抑制PARP-1被认为是一种很有前途的抗癌策略,许多PARP-1目前正在开发和临床评估中。目前,市场上有4种fda批准的PARP-1i,但很少有处于临床开发的最后阶段。所有的分子都是非选择性的PARP-1i。PARP-1i虽然取得了令人鼓舞的成果,但也有其自身的缺点,如安全问题、抗性等。观察PARP-1i在各种实体肿瘤中的成功率,人们迫切需要新型和选择性PARP-1i。本文综述了PARP-1i的研究进展,克服耐药性的方法,以及潜在PARP-1i的新分子的选择性标准。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A review on recent PARP inhibitor advancements in cancer therapy.
Poly [ADP-ribose] polymerase-1 [PARP-1] is a chromatin-bound nuclear enzyme that gets activated by DNA damage, it facilitates DNA repair by binding to DNA breaks and attracting DNA repair proteins to the site of damage. Increased PARP-1 expression is observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. PARP-1 interacts directly, indirectly with various oncogenic proteins and regulates several transcription factors thereby modulating carcinogenesis. There is a lot of pre-clinical and clinical data supporting the use of PARP-1 inhibitors [PARP-1i] in cancers that express homologous recombination deficiencies like mutations within BRCA-1/2 genes. Therapeutic inhibition of PARP-1 is therefore perceived as a promising anticancer strategy and numerous PARP-1i are currently under development and clinical evaluation. Currently, there are 4 FDA-approved PARP-1i in the market, while few are in the last stage of clinical development. All the molecules are non-selective PARP-1i. While giving promising results, PARP-1i have their own disadvantages, like safety problems, resistance, etc. Looking at the success rate of PARP-1i in various solid tumours, there is an urge for novel and selective PARP-1i. In this review, we discuss various aspects related to PARP-1i like recent developments, overcoming the resistance, and selectivity criteria of new molecules for potential PARP-1i.
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来源期刊
Current Enzyme Inhibition
Current Enzyme Inhibition Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
1.30
自引率
0.00%
发文量
30
期刊介绍: Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
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