Molecular Diagnosis in Lung Cancer

The advent of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib and erlotinib has opened a new horizon for the therapeutic options for patients with advanced lung cancer. Treatment paradigms are shifting from cytotoxic chemotherapies to molecular-based targeted therapies. The discovery of somatic mutations in the exons 18 to 21 of the tyrosine kinase (TK) domain of EGFR has revolutionized the understanding of EGFR in lung carcinogenesis and this has opened a new era for the importance of predictive biomarkers to select the treatment of choice and for personalized therapy for lung cancer. Three important EGFR assays are used and these include mutational analysis, fluorescence in situ hybridization and immunohistochemistry. EGFR mutation study seems to be the most important biomarker to predict the response to EGFR-TKI, yet technical standardization for analyzing the status of EGFR mutation is the key factor. Therefore, it is important to standardize the approach and decide which assays are best to predict a patient’s response to targeted therapies. It is also essential to determine the most cost-effective way to integrate EGFR molecular assays into clinical practice. This review will address the practical aspects of each of the currently proposed assays that have focused on EFGR mutational analysis and also the other important molecular markers such as k-ras mutation, the EML4-ALK fusion oncogene, ERCC1 and RRM1.