Nucleotide excision repair pathways involved in Cisplatin resistance in non-small-cell lung cancer.
Nucleotide excision repair pathways involved in Cisplatin resistance in non-small-cell lung cancer.
复制标题
DOI：
10.1177/107327480301000404
复制
发表时间：
2003-07
期刊：
影响因子：
--
通讯作者：
R. Rosell;M. Tarón;A. Barnadas;G. Scagliotti;C. Sarries;B. Roig
中科院分区：
文献类型：
--
作者：
R. Rosell;M. Tarón;A. Barnadas;G. Scagliotti;C. Sarries;B. Roig
背景尽管越来越多的遗传异常被确定参与改变非小细胞肺癌（NSCLC）患者化疗敏感性的DNA修复途径，但尚未开发出用于个体化化疗的翻译测定法。方法在转移性NSCLC中，没有单一的顺铂为基础的化疗方案已被证明上级任何其他。尽管这些研究显示3年生存率尾部较小，但大多数患者的中位生存期为8至10个月。我们回顾了顺铂耐药的主要机制，特别是那些参与核苷酸切除修复（NER）途径（转录偶联修复和全球基因组修复）。结果ERCC 1是一种单链DNA内切酶，与着色性干皮病互补群F形成紧密的异源二聚体。它切割病变5'侧的DNA，如顺铂-DNA加合物。因此，ERCC 1和其他NER酶在卵巢癌顺铂化疗过程中的过度表达似乎与细胞和临床耐药的形成有关。最近，基线ERCC 1 mRNA过表达与顺铂治疗的NSCLC患者的不良反应和生存有关。结论：许多检测方法的证据水平有限，只有ERCC 1 mRNA水平得到了广泛的分析。ERCC 1的影响应在前瞻性临床试验中充分验证。
BACKGROUND In spite of the growing list of genetic abnormalities identified as being involved in DNA repair pathways that alter chemosensitivity in non-small-cell lung cancer (NSCLC) patients, translational assays have not yet been developed for use in individualized chemotherapy. METHODS In metastatic NSCLC, no single cisplatin-based chemotherapy regimen has been shown to be superior to any other. Although these studies show a small survival tail at 3 years, the majority of patients had a median survival of 8 to 10 months. We review the principal mechanisms of cisplatin resistance, particularly those involved in the nucleotide excision repair (NER) pathways (transcription-coupled repair and global genomic repair). RESULTS ERCC1 is a single-stranded DNA endonuclease that forms a tight heterodimer with xeroderma pigmentosum complementation group F. It incises DNA on the 5' side of a lesion such as cisplatin-DNA adduct. Therefore, overexpression of ERCC1 and other NER enzymes during ovarian cancer chemotherapy with cisplatin appears to be implicated in the formation of cellular and clinical drug resistance. Recently, baseline ERCC1 mRNA overexpression has been related to poor response and survival in cisplatin-treated NSCLC patients. CONCLUSIONS The level of evidence for many assays is limited, and only ERCC1 mRNA levels have been analyzed extensively. The impact of ERCC1 should be fully validated in prospective clinical trials.