Olaussen Ken André, Mountzios Giannis, Soria Jean-Charles
Institut de cancérologie Gustave Roussy, Villejuif, France.
Curr Opin Pulm Med. 2007 Jul;13(4):284-9. doi: 10.1097/MCP.0b013e32816b5c63.
Cisplatin-based chemotherapy remains the treatment of choice in advanced nonsmall-cell lung cancer. The development of predictive biomarkers able to identify lung-cancer patients who are most likely to benefit from cisplatin-based chemotherapy would be a powerful tool. Many reports have explored the role of ERCC1 expression in the repair mechanism of cisplatin-induced DNA adducts in cancer cells.
Using immunohistochemistry in resected tumors, the International Adjuvant Lung Cancer Trial showed that high ERCC1 protein expression was associated with improved survival in patients who did not receive chemotherapy. In contrast, the benefit of adjuvant cisplatin-based chemotherapy was more profound in patients with low ERCC1 expression. Other investigators studying mRNA expression in tumor biopsies from patients treated with cisplatin and gemcitabine showed that patients with low ERCC1 mRNA expression have a longer median survival compared to those with high expression.
High ERCC1 expression is predictive of resistance to platinum-based therapy. Thus, there is solid evidence to support ERCC1 as a useful marker of clinical resistance to platinum-based chemotherapy in the adjuvant setting of nonsmall-cell lung cancer. Meanwhile, optimization of methodology and standardization of technical procedures seem necessary before larger prospective studies can address the same question.
基于顺铂的化疗仍然是晚期非小细胞肺癌的治疗选择。开发能够识别最有可能从基于顺铂的化疗中获益的肺癌患者的预测性生物标志物将是一个有力工具。许多报告探讨了ERCC1表达在癌细胞中顺铂诱导的DNA加合物修复机制中的作用。
国际辅助肺癌试验通过对切除肿瘤进行免疫组织化学检测发现，高ERCC1蛋白表达与未接受化疗患者的生存期改善相关。相比之下，ERCC1表达低的患者接受基于顺铂的辅助化疗的获益更大。其他研究人员对接受顺铂和吉西他滨治疗患者的肿瘤活检组织中的mRNA表达进行研究，结果显示，与高表达患者相比，ERCC1 mRNA表达低的患者中位生存期更长。
高ERCC1表达预示着对铂类疗法耐药。因此，有确凿证据支持ERCC1作为非小细胞肺癌辅助治疗中铂类化疗临床耐药的有用标志物。同时，在更大规模的前瞻性研究能够解决相同问题之前，似乎有必要优化方法并规范技术程序。
