Targeted therapies for non-small cell lung cancer: an evolving landscape.
Over the past decade, a multitude of targeted agents have been explored in the treatment of advanced non-small cell lung cancer (NSCLC). Thus far, two broad classes of agents have been implemented in clinical practice: (a) vascular endothelial growth factor (VEGF)-directed therapies and (b) antagonists of the epidermal growth factor receptor (EGFR). In the former category, the agent bevacizumab (a monoclonal antibody) has shown landmark improvements in survival when added to cytotoxic therapy. Small molecule tyrosine kinase inhibitors (TKI) targeting the VEGF receptor (i.e., sunitinib, sorafenib, and vandetanib) show activity in phase II clinical studies. With respect to EGFR-directed therapies, the TKIs gefitinib and erlotinib have shown significant benefit, and have uncovered valuable information about the biology of lung cancer. Outside of therapies directed specifically at VEGF- and EGFR-mediated signaling, trials evaluating insulin-like growth factor-1 receptor (IGF-IR)-targeting agents, cyclooxygenase-2 (COX-2) inhibitors, c-met inhibitors, irreversible pan-HER inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and histone deacetylase (HDAC) inhibitors are ongoing. Inhibitors of ALK show great promise in patients with the relevant gene translocation. Herein, the clinical development of novel therapies for NSCLC is described, including some discussion of relevant biomarkers and determination of synergy with both cytotoxic therapy and other targeted agents.
Pal
Sumanta Kumar
SK
Division of Genitourinary Malignancies, Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USA. spal@coh.org
Figlin
Robert A
RA
Reckamp
Karen
K
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008954:Models, Biological; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor