Biologically targeted treatment of non-small-cell lung cancer: focus on epidermal growth factor receptor.
The epidermal growth factor receptor (EGFR) has emerged in recent years as a key target of molecular therapy for solid tumors. The postembryonic role of EGFR is normally limited. In cancer, however, abnormal EGFR-tyrosine kinase (TK) activity plays a central role in many of the processes involved in tumor progression, such as proliferation, angiogenesis, invasiveness, decreased apoptosis, and loss of differentiation. Several different approaches have been taken to inhibit EGFR-mediated activity in tumor cells, including monoclonal antibodies directed at the ligand-binding portion of the EGFR and small-molecule agents that directly inhibit the intracellular TK domain of EGFR. Two of these TK inhibitors, gefitinib and erlotinib (OSI-774, Tarceva ), have shown antitumor activity and good tolerability across several tumor types in early dose-finding clinical trials, particularly for non-small-cell lung cancer (NSCLC). In heavily pretreated patients with advanced NSCLC, gefitinib showed clinically significant tumor responses and symptom relief with good tolerability. Based on these results, gefitinib has now been approved for the third-line treatment of advanced NSCLC. The use of gefitinib in standard treatment programs or combined with other molecular targeted agents may substantially improve the outlook for patients with NSCLC or other types of solid tumors
Natale
Ronald B
RB
Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA, USA. rnatale@csccc.salick.com
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D066246:ErbB Receptors / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D008024:Ligands; D011799:Quinazolines; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib