EGFR inhibitors in non-small cell lung cancer (NSCLC): the emerging role of the dual irreversible EGFR/HER2 inhibitor BIBW 2992.
Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer and is associated with significant mortality and morbidity worldwide. Despite improvements in conventional treatment for NSCLC, survival remains poor and improvements in patient outcome are warranted. Over recent years, basic scientific research has dramatically increased our knowledge of the pathogenesis of lung cancer and allowed us to uncover and understand the cellular pathways involved in this process. This has led to the development of therapies to selectively target these pathways. Among these, the epidermal growth factor receptor (EGFR) tyrosine kinase family and related downstream pathways play a critical role in cancer development and over recent years have become a validated target in NSCLC. The development of monoclonal antibodies and first-generation tyrosine kinase inhibitors (TKIs) targeted towards EGFR has had a considerable impact on patient outcomes. However, despite dramatic and sustained responses and the discovery of specific patient subgroups that may derive clinical benefit, resistance to first-generation EGFR TKIs inevitably develops. A new generation of agents have been developed to provide superior potency of target inhibition and further individualize the treatment of NSCLC. This article reviews EGFR-targeted therapies currently available for use and undergoing clinical development for the treatment of NSCLC, specifically focusing on next generation agents including BIBW 2992, an irreversible dual inhibitor of EGFR and HER2 kinases.
Spicer
James F
JF
Great Maze Pond, Kings College London, Guy's Hospital Campus, London SE1 9RT, UK. James.spicer@kcl.ac.uk
Rudman
Sarah M
SM
D000077716:Afatinib; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D066246:ErbB Receptors