摘要
自1970年代发现其抗癌活性以来,顺铂和它的类似物已被广泛应用于临床实践,且被用于40%-80%接受化疗的实体瘤患者。这种药物引人入胜的故事在目前仍在继续,包括我们对有关抗癌活性和药物毒性分子机制复杂性理解的进展。虽然基因组DNA已被公认为顺铂最关键的药物靶标,跨多学科的研究成果表明其他靶标和分子相互作用可能与抗癌作用方式、药物毒性和癌细胞对显著抗癌药物抵抗性有关。本文综述了顺铂和非DNA靶标的相互作用,包括在其药理作用和药物毒性范围内的RNAs、蛋白质、磷脂和碳水化合物。其中的一些非DNA靶标和相关机制可能在使用顺铂的肿瘤中以一种高度协调的方式朝向生物结果。因此,对顺铂相互作用复杂性的理解可为调节临床药效或为设计更有效的铂抗癌药物开辟新的途径来促使顺铂在其他癌症治疗应用中重现其在治愈睾丸生殖细胞肿瘤的辉煌。
关键词: Ap4A,BRCA1
图形摘要
Current Cancer Drug Targets
Title:Interactions of Cisplatin with non-DNA Targets and their Influence on Anticancer Activity and Drug Toxicity: The Complex World of the Platinum Complex
Volume: 14 Issue: 9
Author(s): Roman Mezencev
Affiliation:
关键词: Ap4A,BRCA1
摘要: Since the discovery of its anticancer activity in 1970s, cisplatin and its analogs have become widely used in clinical practice, being administered to 40-80% of patients undergoing chemotherapy for solid tumors. The fascinating story of this drug continues to evolve presently, which includes advances in our understanding of complexity of molecular mechanisms involved in its anticancer activity and drug toxicity. While genomic DNA has been generally recognized as the most critical pharmacological target of cisplatin, the results reported across multiple disciplines suggest that other targets and molecular interactions are likely involved in the anticancer mode of action, drug toxicity and resistance of cancer cells to this remarkable anticancer drug. This article reviews interactions of cisplatin with non-DNA targets, including RNAs, proteins, phospholipids and carbohydrates in the context of its pharmacological activity and drug toxicity. Some of these non-DNA targets and associated mechanisms likely act in a highly concerted manner towards the biological outcome in cisplatin-treated tumors; therefore, the understanding of complexity of cisplatin interactome may open new avenues for modulation of its clinical efficacy or for designing more efficient platinum-based anticancer drugs to reproduce the success of cisplatin in the treatment of highly curable testicular germ cell tumors in its therapeutic applications to other cancers.
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Roman Mezencev , Interactions of Cisplatin with non-DNA Targets and their Influence on Anticancer Activity and Drug Toxicity: The Complex World of the Platinum Complex, Current Cancer Drug Targets 2014; 14 (9) . https://dx.doi.org/10.2174/1568009614666141128105146
DOI https://dx.doi.org/10.2174/1568009614666141128105146 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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