肿瘤治疗中的药物再利用

Alkesh Patel
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引用次数: 0

摘要

重新利用或重新定位是指根据多药理学原则,对先前批准的药物在治疗另一种疾病中可能与现有疾病用途相关或不相关的药物进行验证和应用。重新利用的药物在药代动力学、药效学、药物相互作用和毒性参数方面已经有了很好的记录。1962年,沙利度胺对孕妇的治疗导致新生儿光秃化,但在基于抗血管生成特性的基础上,它显示出对多发性骨髓瘤等血液恶性肿瘤的疗效。由于现有药物疗效不明显、治疗费用高、治疗可能降低生活质量、治疗后生存率提高不保证、可能出现复发、肿瘤异质性可能产生耐药等原因,重新利用正成为抗癌药物开发中必不可少的工具。在基于文献的发现、高通量技术、生物信息学多组学方法、副作用和表型的帮助下,可以很好地解决再利用问题。许多监管机构,如EML、NIH和FDA,都在推动重新利用项目,以支持确定现有药物的替代用途。癌症成为主要的健康问题,由于FDA自1990年以来批准的药物数量下降,药物开发产生的巨额费用以及对未来危险负担的预测,通过重新利用来发现有希望的抗癌药物的需求仍然很高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Drug Repurposing in Oncotherapeutics
Repurposing or repositioning means validating and application of previously approved drugs in the treatment of another disease that might be relevant or irrelevant to existing use in disease based on the principle of polypharmacology. Repurposed drugs are already well documented for pharmacokinetic, pharmacodynamic, drug interaction, and toxicity parameters. In 1962, thalidomide treatment in pregnant women led to phocomelia in their newborn but while repurposed based on anti-angiogenesis property, it showed efficacy in hematologic malignancies like multiple myeloma. The repurposing is becoming an essential tool in the anti-cancer drug development due to existing drugs are not effective, high cost of treatment, therapy may degrade the quality of life, improvement of survival after treatment is not guaranteed, relapse may occur, and drug resistance may develop due to tumor heterogeneity. Repurposing can be addressed well with the help of literature-based discovery, high throughput technology, bioinformatics multi-omics approaches, side effects, and phenotypes. Many regulatory bodies like EML, NIH, and FDA promote repurposing programs that support the identification of alternative uses of existing medicines. Cancer becomes the major health issue, and the need to discover promising anti-cancer drugs through repurposing remains very high due to decline in FDA approval since 1990, huge expenses incurred in the drug development and prediction of dangerous future burden.
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