Targeting vascular endothelial growth factor (VEGF)-receptor-signaling in renal cell carcinoma.
Metastatic renal cell carcinoma (RCC) is resistant to conventional chemotherapy. Combined data for a variety of immunotherapies resulted in an overall chance of partial (PR) or complete remission (CR) of only 12.9%. There is a clear need for novel, more effective therapies to prevent relapse, control metastases and improve overall survival. Improved understanding of RCC disease biology has led to the introduction of molecularly targeted treatment strategies in these cancers. Von Hippel-Lindau (VHL) gene inactivation is observed in most clear cell renal carcinoma, resulting in vascular endothelial growth factor (VEGF) over-expression and driving the malignant phenotype. This review discusses the efficacy of novel therapies targeting the VEGF receptor (VEGFR) (e.g. anti-VEGF antibodies, VEGFR tyrosine kinase inhibitors, mTOR inhibitors), some of which were recently approved by the Food and Drug Administration/European Medicines Evaluation Agency (FDA/EMEA) and represent the new treatment standards in RCC patients.
Reuter
Christoph W M
CW
Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Hannover, Germany. christophreuter@yahoo.com
Morgan
Michael A
MA
Grünwald
Viktor
V
Herrmann
Thomas R W
TR
Burchardt
Martin
M
Ganser
Arnold
A
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases; D006623:von Hippel-Lindau Disease / Q000188:drug therapy / Q000235:genetics
D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases