Individualized Therapy Based of Tumoral mRNA Levels of ERCC1, RRM1 and BRCA1 in Advanced Non-Small-Cell Lung Cancer

Advanced stage NSCLC is essentially a fatal disease and treatment is mainly palliative. Systemic cisplatin-based chemotherapy remains the mainstream for the treatment of advanced non-small cell lung cancer (NSCLC) since it improves survival, symptom control and quality of life compared to best supportive care. The selection of appropriate treatment for individual patients remains a challenge in clinical oncology, particularly in the advanced disease. Several lines of evidence indicate that polymorphisms, gene transcripts and gene mutations can play a predictive role and can be used to tailor chemotherapy in different subgroups of cancer patients. There are evidence lead us to use the expression levels of ERCC1 by the tumor as a molecular marker for customized chemotherapy. Another gene, the BRCA1 has a crucial role in DNA repair, since it is implicated in transcription-coupled nucleotide excision repair (TC-NER), leading to radio- and chemo-resistance. RRM1,localized in 11p15.5,also acts as a putative tumor suppressor gene. RRM1 overexpression was related to gemcitabine resistance in human oropharyngeal epidermoid carcinoma KB cells as well as in patients with NSCLC. For those reason we decided to conduct a prospective pilot phase II trial, in patients with wet stage IIIb and IV NSCLC using chemotherapy regimens which will be defined according to the pharmacogenomic profile (tumoral expression of ERCC1, BRCA1 and RRM1) of the tumor cells.