Treatment of nonsmall cell lung cancer:  overcoming the resistance to epidermal growth factor receptor inhibitors.
OBJECTIVE
Testing for epidermal growth factor receptor (EGFR) mutations has become standard practice in treating patients with advanced nonsmall cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are being offered as first-line therapy in patients with EGFR activating mutations. These drugs offer an increased progression-free survival and response rate compared with standard chemotherapy in this setting; however, resistance invariably occurs. This review discusses the development of resistance to EGFR TKIs and the progress that is being made to better understand how to overcome this resistance.


RESULTS
Results from recently published articles dealing with resistance to EGFR TKIs are allowing for a better understanding of this mechanism. No one treatment allows for overcoming this resistance. Understanding this resistance will likely become an individualized patient/tumor approach. Selecting which drug or drugs that may be suitable can only be determined based on the molecular mechanism of resistance.


CONCLUSIONS
Progress is being made in our understanding of the multiple pathways of resistance. Using a tumor molecular signature at the time of progression can determine the best treatment option.
Walter Reed National Military Medical Center, National Cancer Institute, Bethesda, Maryland, USA.
Corey A
CA
Carter
Giuseppe
G
Giaccone
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors