Targeted therapies in non-small cell lung cancer: proven concepts and unfulfilled promises.
Targeted therapies focus on signaling pathways in cancer cells and other molecular processes involved in oncogenesis. Recent approaches affect the following major groups: the epidermal growth factor receptor (EGFR)-family, angiogenesis, the eicosanoid pathway, the PKC/ Ras/ MAPK pathway, the proteasome and inducers of apoptosis. Numerous phase I and II trials have provided promising results and recently, anti-EGFR and anti-VEGF treatments have proven their efficacy in phase III trials. However, others failed in phase III settings (e.g. PKC- and matrix metalloproteinase inhibitors) and it is a moot point, whether patients have been selected properly. The huge amount of new medications raises questions like when to use which strategy in which sequence. The successful implementation of targeted agents into clinical routine will depend on the verification of sufficient predictive markers, allowing their economically reasonable usage. In the current review the up-to-date knowledge concerning targeted therapies in NSCLC is summarized and their therapeutical potential is discussed.
Auberger
Jutta
J
Department of Internal Medicine, Division of Hematology and Oncology, Medical University Innsbruck, Austria.
Loeffler-Ragg
Judith
J
Wurzer
Walter
W
Hilbe
Wolfgang
W
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000068258:Bevacizumab; D001897:Boronic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069286:Bortezomib; D066246:ErbB Receptors; D046988:Proteasome Endopeptidase Complex; D000077156:Gefitinib