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两种可能的吉西他滨药物修饰策略及其对个性化医学的未来贡献。

Two Possible Strategies for Drug Modification of Gemcitabine and Future Contributions to Personalized Medicine.

机构信息

OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.

Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.

出版信息

Molecules. 2022 Jan 4;27(1):291. doi: 10.3390/molecules27010291.

Abstract

Drug repurposing is an emerging strategy, which uses already approved drugs for new medical indications. One such drug is gemcitabine, an anticancer drug that only works at high doses since a portion is deactivated in the serum, which causes toxicity. In this review, two methods were discussed that could improve the anticancer effect of gemcitabine. The first is a chemical modification by conjugation with cell-penetrating peptides, namely penetratin, pVEC, and different kinds of CPP6, which mostly all showed an increased anticancer effect. The other method is combining gemcitabine with repurposed drugs, namely itraconazole, which also showed great cancer cell inhibition growth. Besides these two strategies, physiologically based pharmacokinetic models (PBPK models) are also the key for predicting drug distribution based on physiological data, which is very important for personalized medicine, so that the correct drug and dosage regimen can be administered according to each patient's physiology. Taking all of this into consideration, it is believed that gemcitabine can be repurposed to have better anticancer effects.

摘要

药物重定位是一种新兴策略,它使用已批准的药物来治疗新的医疗适应症。其中一种药物是吉西他滨,这是一种抗癌药物,只有在高剂量下才有效,因为一部分在血清中失活,这会导致毒性。在这篇综述中,讨论了两种可以提高吉西他滨抗癌效果的方法。第一种是通过与穿透肽(如 penetratin、pVEC 和不同种类的 CPP6)缀合进行化学修饰,这大多都显示出了增强的抗癌效果。另一种方法是将吉西他滨与重新定位的药物(如伊曲康唑)联合使用,也显示出了对癌细胞的强大抑制生长作用。除了这两种策略之外,基于生理的药代动力学模型(PBPK 模型)也是基于生理数据预测药物分布的关键,这对于个性化医疗非常重要,以便根据每个患者的生理状况给予正确的药物和剂量方案。考虑到所有这些因素,相信吉西他滨可以被重新定位以产生更好的抗癌效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e2c/8746447/b2127f793e27/molecules-27-00291-g001.jpg

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