Rosell R, Cobo M, Isla D, Camps C, Massuti B
Catalan Institute of Oncology, Barcelona, Spain.
Ann Oncol. 2006 May;17 Suppl 5:v13-16. doi: 10.1093/annonc/mdj942.
Approximately half of lung cancer patients present with metastases, and a large proportion will develop recurrent disease, with median survival to cisplatin-based chemotherapy of 11 months. No predictive factor of response to cisplatin-based chemotherapy is yet available in clinical practice. The nucleotide excision repair system plays a major role in repairing a variety of distorting lesions, notably platinum-induced DNA adducts. ERCC1 is a leading gene in repairing cisplatin DNA damage. We carried out three different studies examining individually the role of ERCC1, RRM1, and then both, mRNA expression in paraffin-embedded pretreatment bronchial biopsies from gemcitabine/cisplatin-treated advanced non-small-cell lung cancer (NSCLC) patients. Median survival was significantly prolonged in patients with low levels of ERCC1 or RRM1. BRCA1 is involved in homologous recombination repair, and we observed that low levels of BRCA1 mRNA significantly increased survival in gemcitabine/cisplatin-treated patients. Our observations lead us to recommend that tumors be regularly assessed for ERCC1 and BRCA1 mRNA expression in order to customize gemcitabine/cisplatin treatment.
大约一半的肺癌患者就诊时已出现转移，并且很大一部分患者会发展为复发性疾病，接受以顺铂为基础的化疗后的中位生存期为11个月。在临床实践中，目前尚无对以顺铂为基础的化疗反应的预测因素。核苷酸切除修复系统在修复各种扭曲性损伤（尤其是铂诱导的DNA加合物）中起主要作用。ERCC1是修复顺铂所致DNA损伤的关键基因。我们开展了三项不同的研究，分别检测了ERCC1、RRM1以及二者的mRNA在接受吉西他滨/顺铂治疗的晚期非小细胞肺癌（NSCLC）患者石蜡包埋的治疗前支气管活检组织中的表达情况。ERCC1或RRM1水平较低的患者中位生存期显著延长。BRCA1参与同源重组修复，我们观察到BRCA1 mRNA水平较低的患者在接受吉西他滨/顺铂治疗后生存期显著延长。我们的观察结果促使我们建议定期评估肿瘤的ERCC1和BRCA1 mRNA表达情况，以便对吉西他滨/顺铂治疗进行个体化调整。
