Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years
Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years
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DOI：
10.3748/wjg.v20.i29.9775
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发表时间：
2014-08-21
影响因子：
4.3
通讯作者：
Panczyk, Mariusz
中科院分区：
文献类型：
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作者：
Panczyk, Mariusz
在过去的二十年中，人类基因组的第一次测序显示了其高度的个体间分化，这是大型国际研究项目（人类基因组计划、千基因组计划国际单体型图计划和基因组应用程序NHLBI-PGA）的结果。这一时期也是分子生物学技术密集发展和癌症生物学知识巨大增长的时期。在临床用于结直肠癌（CRC）患者的治疗中，除了氟嘧啶类药物外，另外两种新的细胞抑制药物被允许使用：伊立替康和奥沙利铂。还对新的治疗方案和用于靶向治疗的新一代药物进行了深入研究。过去 20 年是针对耐药性分子基础的大量体外和体内研究的时期。限制化疗效果的最重要因素之一是癌细胞的原发性和继发性耐药。了解导致肿瘤组织对细胞抑制剂缺乏或低敏感性的遗传因素和机制是当前个性化医疗发展趋势的关键要素。科学家希望通过药物遗传学/药物基因组学的实际应用来提高结直肠癌患者积极治疗反应的百分比。在过去的20年里，不同的预测标志物的临床可用性得到了检验，其中只有少数被证实具有较高的应用潜力。这篇综述是对结直肠癌患者化疗背景下耐药性的综合介绍。所涉及问题的多因素性质和数量不允许作者在一篇评论中对该主题进行全面的研究。 (C) 2014 百事登出版集团有限公司版权所有。
During the past two decades the first sequencing of the human genome was performed showing its high degree of inter-individual differentiation, as a result of large international research projects (Human Genome Project, the 1000 Genomes Project International Hap-Map Project, and Programs for Genomic Applications NHLBI-PGA). This period was also a time of intensive development of molecular biology techniques and enormous knowledge growth in the biology of cancer. For clinical use in the treatment of patients with colorectal cancer (CRC), in addition to fluoropyrimidines, another two new cytostatic drugs were allowed: irinotecan and oxaliplatin. Intensive research into new treatment regimens and a new generation of drugs used in targeted therapy has also been conducted. The last 20 years was a time of numerous in vitro and in vivo studies on the molecular basis of drug resistance. One of the most important factors limiting the effectiveness of chemotherapy is the primary and secondary resistance of cancer cells. Understanding the genetic factors and mechanisms that contribute to the lack of or low sensitivity of tumour tissue to cytostatics is a key element in the currently developing trend of personalized medicine. Scientists hope to increase the percentage of positive treatment response in CRC patients due to practical applications of pharmacogenetics/pharmacogenomics. Over the past 20 years the clinical usability of different predictive markers has been tested among which only a few have been confirmed to have high application potential. This review is a synthetic presentation of drug resistance in the context of CRC patient chemotherapy. The multifactorial nature and volume of the issues involved do not allow the author to present a comprehensive study on this subject in one review. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.