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A Journal on Surgery

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Minerva Chirurgica 2011 October;66(5):483-94

language: English

Resistance to EGFR targeting therapies in lung cancer

Watzka S. B. 1, 2, Posch F. 2, Hochmair M. 3, Setinek U. 4, Köstler W. J. 5, 6, Müller M. R. 1,2

1 Division of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria;
2 Karl Landsteiner Institute for Thoracic Oncology, Otto Wagner Hospital, Vienna, Austria;
3 First Division of Pulmology, Otto Wagner Hospital, Vienna, Austria;
4 Division of Pathology, Otto Wagner Hospital, Vienna, Austria;
5 Division of Oncology, Department of Medicine 1;
6 Comprehensive Cancer Center, Medical University of Vienna, Austria


The treatment of advanced non-small cell lung cancer (NSCLC) by therapies targeting the epidermal growth factor receptor (EGFR) pathway represents one of the most important advances in thoracic oncology. Reversible EGFR tyrosine kinase inhibitors (TKIs), like gefitinib and erlotinib, are able to achieve dramatic responses in a subset of patients. However, most patients treated with TKIs eventually develop resistance against these drugs. Here we review the physiology and pathology of EGFR activation in NSCLC, the clinical experience with TKIs, the mechanisms of resistance against TKIs, and discuss various approaches to treat resistance against TKIs.

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