Tuesday, January 31, 2012

Lung cancer: Molecular pathology and personalized medicine


Mod Pathol. 2012 Jan 27. doi: 10.1038/modpathol.2011.215. [Epub ahead of print]
Molecular pathology of lung cancer: key to personalized medicine.
Cheng L, Alexander RE, Maclennan GT, Cummings OW, Montironi R, Lopez-Beltran A, Cramer HM, Davidson DD, Zhang S.
Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

The majority of lung adenocarcinoma patients with epidermal growth factor receptor- (EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.Modern Pathology advance online publication, 27 January 2012; doi:10.1038/modpathol.2011.215.

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