Molecular mechanisms of signal transduction: epidermal growth factor receptor family, vascular endothelial growth factor family, Kit, platelet-derived growth factor receptor, Ras.
One of the major mechanisms of communication between cells is the binding of polypeptide ligands to cell surface receptors possessing tyrosine kinase (TK) activity. Though many actions of these receptors involve physiological processes, perturbation of TK signaling can result in malignant transformation. During the last few decades, these signaling networks have been studied in detail and finally pharmacological agents targeted at key molecules could be produced. Though many agents have failed, some drugs like bevacizumab, trastuzumab, cetuximab, and erlotinib have already become part of the standard care for common tumors like breast, colorectal, lung, head and neck cancers. Furthermore, imatinib has shown unsurpassed efficacy in the less common, but not less problematic chronic myeloid leukemia and gastrointestinal stromal tumors. Multi-target agents like sunitinib, sorafenib, and lapatinib have already yielded promising results and new agents are being developed. The clinical successes of these agents are unquestionably based on the expanding body of knowledge on the molecular mechanisms that underlie the development and progression of a malignant phenotype. This review will focus on some of the most extensively studied signaling networks like Erb family of receptors, vascular endothelial growth factor (VEGF) and its receptor (VEGFR), Kit, platelet-derived growth factor receptor (PDGFR), and Ras.
Erman
Mustafa
M
Department of Medical Oncology, Hacettepe University, Institute of Oncology, Ankara, Turkey. ermanm@tr.net
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D042442:Vascular Endothelial Growth Factors; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D018631:ras Proteins