文章：

5-氟尿嘧啶：作用机制和临床策略

5-Fluorouracil: mechanisms of action and clinical strategies

原文发布日期：2003-05-01

DOI: 10.1038/nrc1074

类型: Review Article

开放获取: 否

要点：

1. The fluoropyrimidine 5-fluorouracil (5-FU) is an antimetabolite drug that is widely used for the treatment of cancer, particularly for colorectal cancer.
2. 5-FU exerts its anticancer effects through inhibition of thymidylate synthase (TS) and incorporation of its metabolites into RNA and DNA.
3. Modulation strategies, such as co-treatment with leucovorin and methotrexate, have been developed to increase the anticancer activity of 5-FU.
4. Molecular biomarkers that predict tumour sensitivity to 5-FU have been identified, including mRNA and protein expression levels of TS.
5. DNA microarray analysis of 5-FU-responsive genes will greatly facilitate the identification of new biomarkers, novel therapeutic targets and the development of rational drug combinations.

要点翻译：

1. 氟尿嘧啶（5-FU）是一种广泛用于癌症治疗（特别是结直肠癌）的抗代谢药物。
2. 5-FU通过抑制胸苷酸合成酶（TS）并将其代谢产物嵌入RNA和DNA中发挥抗癌作用。
3. 为增强5-FU的抗癌活性，已开发出多种调节策略，例如与亚叶酸钙和甲氨蝶呤的联合给药方案。
4. 目前已有预测肿瘤对5-FU敏感性的分子生物标志物被确认，包括TS的mRNA和蛋白表达水平。
5. 对5-FU应答基因的DNA微阵列分析将极大促进新生物标志物的发现、新治疗靶点的确定以及合理化联合用药方案的开发。

英文摘要：

5-Fluorouracil (5-FU) is widely used in the treatment of cancer. Over the past 20 years, increased understanding of the mechanism of action of 5-FU has led to the development of strategies that increase its anticancer activity. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. Emerging technologies, such as DNA microarray profiling, have the potential to identify novel genes that are involved in mediating resistance to 5-FU. Such target genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy.

摘要翻译： 

5-氟尿嘧啶（5-FU）广泛用于癌症治疗。过去20年，随着对其作用机制的深入了解，已开发出多种增强其抗癌活性的策略。尽管取得这些进展，耐药仍是5-FU临床应用的主要限制。新兴技术如DNA芯片分析有望发现介导5-FU耐药的新基因，这些靶基因可能成为化疗新靶点，或作为5-FU化疗疗效的预测生物标志物，具有潜在治疗价值。

原文链接：

5-Fluorouracil: mechanisms of action and clinical strategies