摘要
癌症是导致我国居民死亡的首要原因,近50年来发病率一直处于上升趋势。5-FU至今仍是治疗乳腺癌、结肠癌、胃癌等肿瘤最常见的药物前体之一,其活性产物能够影响DNA的合成及RNA翻译过程。虽经历年不断改良,但由于越来越多的患者对5-FU产生耐药性,其总体有效率仍不尽如人意。5-FU耐药机制的阐明有利于制定合理的个体化治疗方案、提高治疗效果、改善肿瘤患者预后以及开发新的更有效的抗肿瘤药物。近年来各国研究人员对5-FU的耐药机制、生物调控、前体药物开发、给药方式、疗效判断等的大量研究取得了很多有意义的结果。例如黏蛋白MUC1、DPD基因拷贝数、O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)、热休克蛋白27、40(Hsp27、Hsp40)、表皮生长因子受体8(EGFRv Ⅲ)等与5-FU敏感性降低有关,而OPRT(乳清酸磷酸核糖转移酶)、钙敏受体(CaSR)、5-氯-2,4-二羟基吡啶(CDHP)、前列腺凋亡反应蛋白4(par4)、PG490、罗格列酮、雷帕霉素、基质金属蛋白酶1组织抑制剂(TIMP-1)、酪丝缬肽(YSV)、5-杂氮脱氧胞嘧啶(DAC)、中药复方等可以增加5-FU的化疗敏感性。REG Ⅳ、中间丝蛋白CK-18、胰岛素样生长因子结合蛋白-3(IGFBP-3)、增殖诱导配体/肿瘤坏死因子超家族成员13(APRIL/TNFSF13)等可被作为判断5-FU治疗预后判断的血清学标志物。本文对5-FU作用机制、化疗敏感性影响因子、耐药细胞基因表达谱改变以及可能用于临床5-FU治疗预后判断的血清标志物等领域的最新进展和研究动态作一综述。
5-Fluorouracil （5-FU） is one of the most widely used chemotherapeutic agents for various solid tumors including breast cancer, colorectal cancer （CRC）, and gastric cancer. Unfortunately, some patients have a poor response, possibly owing to clinical resistance of the chemotherapy. Understanding the mechanisms of resistance to 5-FU would allow better selection of patients for 5-FU therapy and allow personalized therapeutics to be designed to overcome resistance. Recently there have been many studies done and much progress made in 5-FU biological control, pro-drug development and delivery methods. For example, MUC1, dihydropyrimidine dehydrogenase, O-6-methylguanine-DNA methyltransferase, Heat shock protein 27, Heat shock protein 40, Epidermal growth factor receptor viii, and others have been found to be related to low 5-FU efficacy. On the other hand orotate phosphoribosyltransferase, calcium-sensing receptor, 5-chloro-2, 4-dihydroxypyridine, prostate apoptosis response protein 4, tissue inhibitor of matrix-metalloproteinases 1, tyroservatide, 5-azadeoxycytidine, PG490, Rosiglitazone, Rapamycin, and various herbal medicines have been found to promote 5-FU ef- ficacy. There are also several serum biomarkers for monitoring the treatment response of 5-FU including regenerating islet-derived family member 4, insulin-like growth factor binding protein 3, a proliferation-inducing ligand/tumor necrosis factor superfamily, and TNFSF13. The latest progress in understanding the molecular mechanisms of 5-FU resistance and sensitivity and identifying predictive biomarkers, as well as developing research trends, are reviewed in this paper.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第21期1255-1259,共5页
Chinese Journal of Clinical Oncology
关键词
肿瘤
5-FU
疗效
Neoplasm
Fluorouracil
Treatment efficacy
