Rosell Rafael, Cobo Manuel, Isla Dolores, Sanchez Jose Miguel, Taron Miquel, Altavilla Giuseppe, Santarpia Mariacarmela, Moran Teresa, Catot Silvia, Etxaniz Olatz
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Badalona, Barcelona, Spain.
Lung Cancer. 2005 Dec;50 Suppl 2:S33-40.
Cisplatin-based chemotherapy has long been the cornerstone of non-small cell lung cancer (NSCLC) management. However, median survival rarely exceeds 1 year. The identification of molecular markers can help to predict response, leading to a broad implementation of the new concept of customized chemotherapy. ERCC1 is an excision nuclease within the nucleotide excision repair pathway that forms a heterodimer with XPF. As a unit, they execute the 5' incision into the DNA strand relative to the site of DNA damage. The 5' excision is the last of several steps that are specific to excision of a platinum DNA lesion. In mouse models, normal ERCC1 function is critical to normal aging and brain development. Numerous studies indicate that ERCC1 influences the repair of platinum DNA damage. We report here our accumulated experience of ERCC1 mRNA expression and outcome in cisplatin-treated NSCLC patients and the preliminary confirmatory data on a prospective ERCC1 mRNA customized docetaxel-cisplatin trial, in which low ERCC1 mRNA levels in the tumor correlate with significantly better response. ERCC1 is one of several proteins involved in the repairosome, where other DNA repair genes, such as BRCA1, are also central to cisplatin resistance.
以顺铂为基础的化疗长期以来一直是非小细胞肺癌（NSCLC）治疗的基石。然而，中位生存期很少超过1年。分子标志物的识别有助于预测反应，从而推动定制化疗这一新概念的广泛应用。ERCC1是核苷酸切除修复途径中的一种切除核酸酶，它与XPF形成异二聚体。作为一个单位，它们相对于DNA损伤位点在DNA链上进行5'切口。5'切除是切除铂类DNA损伤特有的几个步骤中的最后一步。在小鼠模型中，正常的ERCC1功能对正常衰老和大脑发育至关重要。大量研究表明，ERCC1影响铂类DNA损伤的修复。我们在此报告我们在顺铂治疗的NSCLC患者中关于ERCC1 mRNA表达和预后的累积经验，以及一项前瞻性ERCC1 mRNA定制多西他赛 - 顺铂试验的初步验证数据，其中肿瘤中低水平的ERCC1 mRNA与显著更好的反应相关。ERCC1是参与修复体的几种蛋白质之一，其中其他DNA修复基因，如BRCA1，也是顺铂耐药的关键因素。
