Applications of genomics in NSCLC

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.