Abstract
Thoracic oncologists traditionally have made treatment decisions based upon tumor histology, distinguishing non-small cell lung cancer (NSCLC) from small cell lung cancer (SCLC). However, recent data has revealed that at least one histological subtype of NSCLC, lung adenocarcinoma comprises multiple molecularly distinct diseases. Lung adenocarcinoma subsets now can be defined by specific 'driver' mutations in genes encoding components of the EGFR signaling pathway. Importantly, these mutations have implications regarding targeted therapy. Here, we focus on EGFR mutant NSCLC-a prime example of a clinically relevant molecular subset of lung cancer, with defined mechanisms of drug sensitivity, primary drug resistance, and acquired resistance to EGFR tyrosine kinase inhibitors. Efforts are now being made to overcome mechanisms of acquired resistance. These findings illustrate how knowledge about the genetic drivers of tumors can lead to rational targeted therapy for individual patients.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / chemistry
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / enzymology
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Carcinoma, Non-Small-Cell Lung / genetics
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Clinical Trials as Topic
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Drug Resistance, Neoplasm*
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / genetics
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Erlotinib Hydrochloride
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Gefitinib
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HSP90 Heat-Shock Proteins / antagonists & inhibitors
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Humans
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Molecular Targeted Therapy / methods
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Mutation
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology
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Protein Structure, Tertiary
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Quinazolines / pharmacology
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Quinolines / pharmacology
Substances
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Antineoplastic Agents
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HSP90 Heat-Shock Proteins
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Protein Kinase Inhibitors
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Quinazolines
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Quinolines
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Erlotinib Hydrochloride
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ErbB Receptors
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neratinib
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Gefitinib