Biomarkers for the targeted therapies of non-small cell lung cancer
Antonio Rossi1, Domenico Galetta2
1Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy; 2Department of Medical Oncology, Giovanni Paolo II Oncology Institute, Bari, Italy
Abstract: Targeted therapy includes new biologic agents specifically designed to selectively target molecular pathways responsible for, or that substantially drive, the malignant phenotype of cancer cells. A lot of new biologic agents have been introduced in clinical development for the treatment of advanced non-small cell lung cancer (NSCLC), but unfortunately negative results were more frequent than successes. Two pathways have been deeply studied and have led to the development of corresponding biomarkers for defining the most appropriate therapeutic approach in advanced NSCLC patients. The epidermal growth factor receptor (EGFR) pathway is targeted by tyrosine kinase inhibitors, gefitinib and erlotinib, and monoclonal antibody, cetuximab. EGFR mutation status, EGFR gene copy number determined by fluorescent in situ hybridization, and EGFR protein expression determined by immunohistochemistry have been evaluated as potential markers for clinical decision making regarding anti-EGFR therapy. Among these, EGFR mutation status resulted in the most important predictive/prognostic factor for EGFR-tyrosine kinase inhibitor therapy. EGFR protein expression seems to be important for cetuximab plus chemotherapy treatment, but further data are needed to define its role in this setting. In the last few years, the anaplastic lymphoma kinase (ALK) gene fusion is becoming an important biomarker in defining the specific NSCLC subtype to target with the corresponding inhibitor, crizotinib. To date, considering the EGFR activating mutations and the ALK gene fusion, generally mutually exclusive, and the availability of the correspondent inhibitors, 20% to 50% of advanced NSCLC could now be treated in Western and Eastern countries, respectively, with a targeted therapy.
Keywords: biomarkers, EGFR, ALK, NSCLC, TKI, crizotinib
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