Institute of Tumour Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
EPMA J. 2010 Sep;1(3):485-94. doi: 10.1007/s13167-010-0022-5. Epub 2010 Jun 4.
The 5-fluorouracil (5-FU)-based chemotherapy is a standard treatment for patients with colorectal cancer. However, a relevant number of patients suffer from severe toxic side effects, such as haemotoxicity, while lacking clinical response to adjuvant therapy. The inter-individual variations of drug toxicity and efficacy of the pyrimidine antagonist observed in clinical practice are mainly determined by genetic polymorphisms. The screening of genotypes, such as thymidylate synthase, dihydropyrimidine dehydrogenase, methylene tetrahydrofolate reductase, orotate phosphoribosyltransferase or glutathione S-transferase, could help identifying those patients with colorectal carcinoma who can actually benefit from a 5-FU-based therapy. The current chapter elucidates the roles of the polymorphisms in the enzymes involved in the 5-FU metabolic pathway as prognostic and predictive markers. It reports on the relationship between various genotypes in patients with colorectal carcinoma and their responsiveness to a 5-FU-based chemotherapy, and concludes with an outlook on possible future directions in treatment of colorectal cancer.
5-氟尿嘧啶（5-FU）为基础的化疗是结直肠癌患者的标准治疗方法。然而，相当数量的患者因严重的毒性副作用而受苦，如血液毒性，同时对辅助治疗缺乏临床反应。在临床实践中观察到的嘧啶拮抗剂的药物毒性和疗效的个体间差异主要由遗传多态性决定。对胸苷酸合成酶、二氢嘧啶脱氢酶、亚甲基四氢叶酸还原酶、乳清酸磷酸核糖基转移酶或谷胱甘肽 S-转移酶等基因型的筛选，可以帮助确定那些实际上可以从 5-FU 为基础的治疗中获益的结直肠癌患者。本章阐述了参与 5-FU 代谢途径的酶的多态性作为预后和预测标志物的作用。报告了结直肠癌患者中各种基因型与对 5-FU 为基础化疗的反应性之间的关系，并对结直肠癌治疗的可能未来方向进行了展望。
