Predictive biomarkers with potential of converting conventional chemotherapy to targeted therapy in patients with metastatic colorectal cancer
Predictive biomarkers with potential of converting conventional chemotherapy to targeted therapy in patients with metastatic colorectal cancer
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DOI：
10.3109/00365521.2012.640835
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发表时间：
2012-03-01
影响因子：
1.9
通讯作者：
Brunner, Nils
中科院分区：
文献类型：
--
作者：
Jensen, Niels Frank;Smith, David Hersi;Brunner, Nils
转移性结直肠癌（mCRC）患者全身化疗方案的可用性是基于大型前瞻性随机研究的结果。用于治疗mCRC的主要化疗药物是氟尿嘧啶（5-氟尿嘧啶（5-FU）;卡培他滨）联合奥沙利铂（FOLFOX）或伊立替康（FOLFIRI）。任一联合治疗的客观缓解率约为50%，其中未观察到无进展生存期或总生存期的显著差异。有趣的是，许多临床前和临床研究表明，基于奥沙利铂和基于伊立替康的治疗之间缺乏完全交叉耐药性。因此，某些mCRC患者亚群可能从一种药物组合中获益更多。为了解决这一临床问题，人们一直非常关注这三种药物的预测性生物标志物的开发和验证。在此，我们对5-FU、奥沙利铂和伊立替康治疗转移性结直肠癌患者的预测性生物标志物的现状进行了全面综述。总体结论如下：鉴定了几种有希望的生物标志物候选物，特别是5-FU的胸苷酸合成酶、伊立替康的拓扑异构酶I和奥沙利铂的ERCC 1。然而，这些候选药物需要进一步分析，其中检测性能和临床试验设计应成为重点。
The availability of systemic chemotherapy regimens for the treatment of patients with metastatic colorectal cancer (mCRC) is based on the results from large prospective, randomized studies. The main chemotherapeutic drugs used in treatment of mCRC are the fluoropyrimidines (5-fluorouracil (5-FU); capecitabine) in combination with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). The objective response rate to either combination is approximately 50%, where no significant differences with regard to progression free survival or overall survival have been observed. Interestingly, a number of preclinical and clinical studies have indicated lack of full cross resistance between oxaliplatin based and irinotecan based treatment. Therefore, it is possible that certain mCRC patient subpopulations would benefit more from one drug combination rather than the other. To address this clinical problem there has been much focus on development and validation of predictive biomarkers for these three drugs. Here, we present a thorough review on the current status of predictive biomarkers for 5-FU, oxaliplatin and irinotecan treatment of mCRC patients. The overall conclusions were as follows: Several promising biomarker candidates were identified, notably thymidylate synthase for 5-FU, topoisomerase I for irinotecan and ERCC1 for oxaliplatin. However, these candidates warrant further analysis, where assay performance and clinical trial design should be in focus.