Title: The Potential Role of Pharmacogenomic and Genomic in the Adjuvant Treatment of Early Stage Non Small Cell Lung Cancer
Volume: 9
Issue: 4
Author(s): Clorinda Schettino, Maria A. Bareschino, Paolo Maione, Antonio Rossi, Fortunato Ciardiello and Cesare Gridelli
Affiliation:
Keywords:
NSCLC, adjuvant treatment, molecular markers, ERCC1, RRM1, β-tubulin, EGFR
Abstract: Although notable progress has been made in the treatment of non-small-cell lung cancer (NSCLC) in recent years, this disease is still associated with a poor prognosis. Despite early-stage NSCLC is considered a potentially curable disease following complete resection, the majority of patients relapse and eventually die after surgery. Adjuvant chemotherapy prolongs survival, altough the absolute improvement in 5-year overall survival is only approximately 5%. Trying to understand the role of genes which could affect drug activity and response to treatment is a major challenge for establishing an individualised chemotherapy according to the specific genetic profile of each patient. Among genes involved in the DNA repair system, the excision repair cross-complementing 1 (ERCC1) is a useful markers of clinical resistance to platinum-based chemotherapy. In the International Lung Cancer Trial (IALT) adjuvant chemotherapy significantly prolonged survival among patients with ERCC1 negative tumors but not among ERCC1-positive patients. BRCA1 and ribonucleotide reductase M1 (RRM1), two other key enzymes in DNA synthesis and repair, appear to be modulators of drug sensitivity and may provide additional information for customizing adjuvant chemotherapy. Several clinical trials suggest that overexpression of class III β-tubulin is an adverse prognostic factor in cancer since it could be responsible for resistance to anti-tubulin agents. A retrospective analysis of NCIC JBR.10 trial showed that high tubulin III expression is associated with a higher risk of relapse following surgery alone but also with a higher probability of benefit from adjuvant cisplatin plus vinorelbine chemotherapy. Finally, the use of gene expression patterns such as the lung metagene model could provide a potential mechanism to refine the estimation of a patients risk of disease recurrence and could affect treatment decision in the management of early stage of NSCLC. In this review we will discuss the potential role of pharmacogenomic approaches to guide the medical treatment of early stage NSCLC.
