Authors: William Pao
Publish Date: 2006/11/09
Volume: 58, Issue: 1, Pages: 11-15
Abstract
The epidermal growth factor receptor EGFR tyrosine kinase inhibitors TKIs gefitinib and erlotinib induce dramatic responses in certain patients with nonsmall cell lung cancer NSCLC As such the drugs provide an unexpected tool to dissect clinically relevant molecular subsets of NSCLC For example using mutational profiling of tumor DNA from patients with sensitivity primary resistance and secondary resistance to these agents we and others have demonstrated that somatic mutations in the tyrosine kinase domain of EGFR are associated with sensitivity to gefitinib and erlotinib while mutations in KRAS which encodes a GTPase downstream of EGFR are associated with primary resistance Furthermore second site mutations in the EGFR kinase domain are commonly found in patients with acquired resistance We are now using a variety of molecular and biological approaches to help further define molecular subsets of lung cancer that have relevance in the clinicThe author acknowledges all the members of the MSKCC Lung Cancer Oncogenome Group the patients who consented for participation in these studies and for funding the Joan’s Legacy Foundation the Doris Duke Charitable Foundation NIH and an anonymous donor
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