Targeting multiple signal transduction pathways in lung cancer.
Growth factor signals are propagated from the cell surface to intracellular processes that control critical functions such as growth, differentiation, angiogenesis, and inhibition of apoptosis via sequential kinase signaling. These kinases are receptor kinases, which are transmembrane proteins such as epidermal growth factor receptor or cytoplasmic kinases such as Src kinase. In malignancies, these signaling pathways are often exploited to optimize tumor growth and metastasis. Thus, they represent attractive targets for cancer therapy. This review will summarize current knowledge of the small-molecule multiple-kinase inhibitors in lung cancer therapy. These inhibitors generally hinder the phosphorylation of several protein kinases of membrane receptors, such as vascular endothelial growth factor receptors, platelet-derived growth factor receptors, the human epidermal growth factor receptor family, and cytoplasmic receptors such as c-Kit, Raf kinase, and FLT3. These inhibitors include ZD6474, SU11248, AEE 788, sorafenib, vatalanib, and AG-013736.
Adjei
Alex A
AA
Division of Medical Oncology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA. adjei.alex@mayo.edu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
D000970:Antineoplastic Agents; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A