关键词: Gemcitabine cytarabine cytidine deaminase deoxycytidine kinase hENT1 ribonucleotide reductase

来  源:   DOI:10.1080/15257770.2023.2272640

Abstract:
UNASSIGNED: Cytotoxic nucleosides (gemcitabine, cytarabine…) are used for the treatment of various malignancies. Their activity is dependent on the interaction with several proteins and enzymes of nucleotide metabolism. It has for a long time been hypothesized that the clinical activity of nucleoside analogues can be predicted by studying corresponding genes or gene products in clinical samples.
UNASSIGNED: In this short review, I will present old and new published data from our group and others about the prediction of activity of these drugs concentrating on gene-candidate approaches, and discuss biological and technical limitations of these.
UNASSIGNED: A large number of studies have been conducted in various clinical settings (drugs, disease, patient cohort…) evaluating DNA, mRNA or protein-related markers. Although some individual parameters and associations thereof have been validated, only a very few numbers have been implemented in pretreatment evaluations of patients.
UNASSIGNED: There is still much to do in the field of outcome-prediction with nucleoside analogues. The use of multiparametric methods could increase the success rate but at the cost of a poorer understanding of molecular mechanisms.
摘要:
细胞毒性核苷(吉西他滨,阿糖胞苷...)用于治疗各种恶性肿瘤。它们的活性取决于与几种蛋白质和核苷酸代谢酶的相互作用。长期以来一直假设核苷类似物的临床活性可以通过研究临床样品中的相应基因或基因产物来预测。
在这篇简短的评论中,我将展示我们小组和其他人发表的新旧数据,这些数据是关于这些药物的活性预测,集中在基因候选方法上,并讨论这些的生物学和技术局限性。
在各种临床环境中进行了大量研究(药物,疾病,患者队列...)评估DNA,mRNA或蛋白质相关标记。尽管已经验证了一些单独的参数及其关联,在患者的预处理评估中,仅实施了极少数数字.
在核苷类似物的结果预测领域还有很多工作要做。使用多参数方法可以提高成功率,但代价是对分子机制的理解较差。
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