Determinants of chemosensitivity in gastric cancer
Determinants of chemosensitivity in gastric cancer
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DOI：
10.1016/j.coph.2006.05.002
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发表时间：
2006-08-01
影响因子：
4
通讯作者：
Lenz, Heinz-Josef
中科院分区：
文献类型：
--
作者：
Park, David J.;Lenz, Heinz-Josef
胃癌管理的最新进展，特别是在化疗的竞技场中，正在为最大化有效性同时最小化毒性的最优化治疗铺平道路。化学治疗设备的扩展导致了细胞毒性剂的多种组合。不幸的是，化疗的益处充其量是适度的，并且在比较性III期试验中没有一种组合显示出明显优于其他组合。正是在这种背景下，药物遗传学的进步有可能通过前瞻性预测特定方案的临床获益，在不同患者亚群中实现上级临床结局方面发挥重要作用。我们刚刚开始在胃癌药物遗传学方面取得进展，主要是通过小规模的试点回顾性研究。到目前为止，已经确定了几个潜在的候选者，如胸苷酸合成酶，切除修复互补组1和谷胱甘肽S-转移酶P1，并且更多的被结合到表面，特别是当生物疗法被添加到医疗设备时。鉴于细胞毒性代谢的复杂性质，未来将面临严峻的挑战，多个参与者共同影响药物有效性和/或毒性。需要精心设计的大型前瞻性试验来确定多个潜在候选基因中的关键基因，这些基因可以帮助临床医生根据患者的药物遗传学特征就特定方案做出实时治疗决策。
Recent advances in the management of gastric cancer, especially in the arena of chemotherapy, are paving the way for optimization of treatment that maximizes effectiveness while minimizing toxicity. The expansion of the chemotherapeutic armamentarium has led to multiple combinations of cytotoxic agents. Unfortunately, the benefit of chemotherapy has been modest at best, and no one combination has shown significant superiority over the others in comparative Phase III trials. It is in this setting that pharmacogenetic advances have the potential to play an important role in achieving superior clinical outcome among different subsets of patients through prospective prediction of clinical benefit to particular regimens. We are just beginning to make inroads in gastric cancer pharmacogenetics, mostly through small, pilot retrospective studies. Several potential candidates, such as thymidylate synthase, excision repair complementation group 1 and glutahione S-transferase P1, have been identified so far and more are bound to surface, especially when biologic therapies are added to the armamentarium. Serious challenges lay ahead given the complex nature of cytotoxic metabolism with multiple players working together to influence drug effectiveness and/or toxicity. Well-designed large prospective trials are needed to identify key genes among the multiple potential candidates that can help a clinician make real-time treatment decisions in respect to a particular regimen depending on a patient's pharmacogenetic profile.