小说fluoropyrimidines:提高细胞毒性治疗的疗效和耐受性。
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小RD,卡西迪J
小说fluoropyrimidines:提高细胞毒性治疗的疗效和耐受性。
咕咕叫抗癌药物目标。2004年3月,4 (2):191 - 204。
- PubMed ID
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15032669 (在PubMed]
- 文摘
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fluoropyrimidines是第一个合成近50年前,合理设计抗癌剂。他们的目标是嘧啶,因此DNA合成。5 -氟尿嘧啶是最广泛用于各种恶性肿瘤。近年来更全面的了解这些药物的药物代谢动力学情况导致他们利用更有效的和通用的抗癌药物比最初设想。这部分发生由于识别计划的依赖性疗效的研究者用甲酰四氢叶酸和调制的活动。然而小说的发展fluropyrimidines capcetabine等UFT, eniluracil可口服药物,提供了平等的如果不是卓越的功效与改进的耐受性和病人接受。现在认识到,酶多态性的关键分子的表达和异质性的重要决定因素这些药物的药代动力学和药效学效应处理在个别病人。进一步描述这样的inter-individual inter-tumoral可变性,例如在酶如DPD和胸苷磷酸化酶还在继续。这项工作提供了改进的承诺在疗效和耐受性的过程总是化疗(病人和肿瘤)。与药物动力学的理解的进步,那么进展Fluropyrimidine药效学。 The inhibition of thymidylate synthetase by dFUMP and thereby dTMP and DNA synthesis is thought to be the critical mechanism. The incorporation of FUTP and dFUTP into RNA and DNA are also postulated to be of importance. While these events have been well defined, exactly how they lead to cell death is less clearly understood. Similarly, the mechanism of selective cancer cell cytotoxicity is not well understood. Pharmacokinetics and cell cycle kinetics provide a partial explanation. There is some evidence to suggest that the most important factor in determining cytotoxicity is the cellular response to fluoropyrimidine induced biochemical abnormalities rather than the lesions themselves. In this hypothesis the difference in response between normal and cancer cells is of critical importance. Further improvements in efficacy and tolerability could be made by elucidation of the molecular mechanisms behind this process. This knowledge in combination with the advances already made (and ongoing) in pharmacokinetics may allow the full potential of fluoropyrimidines as anti-cancer agents to be realised in the future.