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Current Respiratory Medicine Reviews

Editor-in-Chief

ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Role of Tyrosine Kinase Inhibitor Molecules in Non Small Cell Lung Cancer:From Benchside to Bedside

Author(s): Alessia Catassi, Alfredo Cesario, Pierluigi Granone and Patrizia Russo

Volume 3 , Issue 2 , 2007

Page: [159 - 167] Pages: 9

DOI: 10.2174/157339807780599135

Price: $65

Abstract

The human epidermal growth factor receptor (EGFR) biology is not completely explained; however EGFRtargeting has formed the basis of extensive and growing drug development. Inhibition of receptor tyrosine kinase activity involved in the EGFR signalling cascade is a fundamental mechanism for the use of EGFR specific tyrosine kinase (TK) inhibitors exemplified by gefitinib (ZD1839, Iressa) and erlotinib (OSI-774, Tarceva). Despite initially promising results in chemotherapy-resistant patients with non small cell lung cancer (NSCLC), disappointing results from phase III trials of gefitinib in NSCLC have been of concern of some. When EGFR-targeting drugs were introduced into the clinic, the specific targets affected in human tumors were unknown. Recently, different studies reported that mutations in the TK domain of EGFR are strongly associated with gefitinib- or erlotinib-sensitivity in patients with NSCLC. This article reviews the rationale for targeting EGFR by TK inhibitors, the discovery of EGFR mutations and subsequent studies to define the incidence, spectrum and functions of EGFR mutations. This paper represents the effort of a lung cancer focused translational research team made up of molecular biologists, medical oncologists and thoracic surgeons. The final objective is to achieve a comprehensive, but simple, review of the current status of the shift from cytotoxic to molecularly targeted therapy in lung cancer treatment potentially useful in the planning of translational research trials.

Keywords: EGFR family, Non-small cell lung cancer (NSCLC), cell proliferation, Gefitinib, OSI-774


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