Personalizing Therapy with Targeted Agents in Non-Small Cell Lung Cancer

Rodrigo Dienstmann 1 , Pablo Martinez 2 , Enriqueta Felip 2 1 Molecular Therapeutic Research Unit, Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona 2 Thoracic Neoplasms Unit, Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona Received: March 12, 2011; Accepted: March 23, 2011; Published: March 23, 2011; Keywords: ALK, EGFR, KRAS, lung cancer, targeted therapy Correspondence: Enriqueta Felip, e-mail: // // Abstract In the last 6 years, since the first reports of an association between somatic mutations in epidermal growth factor receptor ( EGFR ) exons 19 and 21 and response to EGFR tyrosine kinase inhibitors (TKIs), treatment of non-small cell lung cancer (NSCLC) has changed dramatically. Based on laboratory and clinical observations, investigators have anticipated that these mutations could be predictive of response to EGFR TKIs and numerous studies have confirmed that the presence of mutation was associated with longer survival in patients receiving targeted therapy. Prospective trials comparing standard platinum-based chemotherapy with EGFR TKIs in patients with and without activating EGFR mutations validated the predictive value of molecular selection of patients for first-line treatment of advanced NSCLC. Recently, preclinical and first-in-human studies have demonstrated impressive activity of ALK TKI in tumors harboring ALK rearrangement. In this article, we review current data on molecular biology of lung cancer and evidence-based patient selection for targeted therapy.