Furuta Takahisa
Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashiku, Hamamatsu 431-3192, Japan.
J Gastroenterol. 2009;44(10):1016-25. doi: 10.1007/s00535-009-0124-9.
The study of pharmacogenomics (PGx) has recently been intensively applied to gastrointestinal tract cancer. It has become clear that there are genetic differences in the activities of enzymes that influence the kinetics of chemotherapeutic agents. Moreover, genetic differences related to cellular sensitivity to anti-cancer agents have also been elucidated. In GI-tract cancer chemotherapy, 5-FU, gemcitabine, taxanes (docetaxel and paclitaxel), platinum (cisplatin and oxaliplatin) and irinotecan are often used, and molecular targeting therapy has also been developed. The respective PGx markers to such agents have been reported. Of the candidate PGx markers, K-ras mutation and UGT1A1 polymorphisms have sufficient evidence to justify routine clinical assessment for the selection of anti-cancer regimens. Progress in this field would facilitate the further development of PGx-guided individualized therapy, which could be expected to increase therapeutic efficacy and decrease the risk of adverse events.
药物基因组学(PGx)的研究最近已被广泛应用于胃肠道癌。很明显,影响化疗药物动力学的酶的活性存在基因差异。此外,与细胞对抗癌药物的敏感性相关的基因差异也已得到阐明。在胃肠道癌化疗中,常使用5-氟尿嘧啶、吉西他滨、紫杉烷类(多西他赛和紫杉醇)、铂类(顺铂和奥沙利铂)和伊立替康,并且分子靶向治疗也已得到发展。已报道了针对这些药物各自的PGx标志物。在候选PGx标志物中,K-ras突变和UGT1A1多态性有足够的证据证明进行常规临床评估以选择抗癌方案是合理的。该领域的进展将有助于PGx指导的个体化治疗的进一步发展,有望提高治疗效果并降低不良事件的风险。