Abstract

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including lung malignancies. Gefitinib and erlotinib are two available therapeutics that act as specific inhibitors of tyrosine kinase (TK) domains. We performed a case-control study with formalin-fixed paraffin-embedded tissue blocks (FFPE) from tissue biopsies of 167 non-small cell lung carcinoma (NSCLC) patients and 167 healthy controls. The tissue biopsies were studied for mutations in exons 18-21 of the EGFR gene. This study was performed using PCR followed by DNA sequencing. We identified 63 mutations in 33 men and 30 women. Mutations were detected in exon 19 (delE746-A750, delE746-T751, delL747-E749, delL747-P753, delL747-T751) in 32 patients, exon 20 (S786I, T790M) in 16, and exon 21 (L858R) in 15. No mutations were observed in exon 18. The 63 patients with EFGR mutations were considered for upfront therapy with oral tyrosine kinase inhibitor (TKI) drugs and have responded well to therapy over the last 15 months. The control patients had no mutations in any of the exons studied. The advent of EGFR TKI therapy has provided a powerful new treatment modality for patients diagnosed with NSCLC. The study emphasizes the frequency of EGFR mutations in NSCLC patients and its role as an important predictive marker for response to oral TKI in the south Indian population.

Highlights

  • Lung Cancer is the most common cancer and the leading cause of cancer death in the world

  • The advent of Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy has provided a powerful new treatment modality for patients diagnosed with non-small cell lung carcinoma (NSCLC)

  • We aimed to identify the impact of EGFR mutational status on the risk of lung cancer, and the NSCLC patients’ clinical outcome when treated with oral EGFR-TKI

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Summary

Introduction

Lung Cancer is the most common cancer and the leading cause of cancer death in the world. This is true in India, where cancer accounts for 28% of the total number of deaths. The incidence of lung cancer in Asia has become the greatest threat to human health (Varalakshmi et al, 2013; Zhao et al, 2014). Other known carcinogens related to lung cancer are radon, arsenic, cadmium, chromates, and asbestos (Wang et al, 2014). Adenocarcinoma, squamous cell carcinoma, and small-cell carcinoma are three major forms of lung cancers. The pivotal role of genetics in cancer predisposition, especially in the most malignant lung cancers, has prompted substantial interest in recent years (Jin et al, 2014)

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