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结直肠癌中切除修复交叉互补基因 1 的研究综述。

A review of excision repair cross-complementation group 1 in colorectal cancer.

机构信息

Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA.

出版信息

Clin Colorectal Cancer. 2011 Sep;10(3):157-64. doi: 10.1016/j.clcc.2011.03.024. Epub 2011 Apr 28.

Abstract

Oxaliplatin-based chemotherapy is the standard of care in patients with high-risk stage II and stage III colorectal cancer as well as in patients with advanced disease. Unfortunately, a large proportion of patients offered oxaliplatin fail to benefit from it. In the era of personalized treatment, there are strong efforts to identify biomarkers that will predict efficacy to oxaliplatin-based treatments. Excision repair cross-complementation group 1 (ERCC1) is a key element in the nucleotide excision repair (NER) pathway, which is responsible for repairing DNA adducts induced by platinum compounds. ERCC1 has recently been shown to be closely associated with outcome in patients with non-small-cell lung cancer (NSCLC): both high ERCC1 protein and gene expression are associated with resistance to cisplatin-based chemotherapy and better outcome without treatment. Therefore, ERCC1 has the potential to be used as a strong candidate biomarker, both predictive and prognostic, for colorectal cancer. This review will focus on the preclinical and clinical evidences supporting ERCC1 as a major molecule in oxaliplatin resistance. In addition, the important technologies used to assess ERCC1 gene and protein expression will be highlighted.

摘要

奥沙利铂为基础的化疗是高危 II 期和 III 期结直肠癌患者以及晚期疾病患者的标准治疗方法。不幸的是,很大一部分接受奥沙利铂治疗的患者并未从中获益。在个性化治疗时代,人们正在努力寻找能够预测奥沙利铂治疗效果的生物标志物。切除修复交叉互补组 1(ERCC1)是核苷酸切除修复(NER)途径中的一个关键元素,负责修复铂类化合物诱导的 DNA 加合物。最近的研究表明,ERCC1 与非小细胞肺癌(NSCLC)患者的预后密切相关:ERCC1 蛋白和基因表达水平均较高与顺铂为基础的化疗耐药和无治疗时的更好预后相关。因此,ERCC1 有可能成为结直肠癌的一种强有力的候选生物标志物,兼具预测和预后价值。这篇综述将重点介绍支持 ERCC1 作为奥沙利铂耐药主要分子的临床前和临床证据。此外,还将强调评估 ERCC1 基因和蛋白表达的重要技术。

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