Kinase targets in renal-cell carcinomas: reassessing the old and discovering the new.
Renal-cell carcinoma is a heterogeneous group of tumours that arise in the adult kidneys. Irrespective of the type of renal tumour, traditional chemotherapeutic and radiation-based therapies have been largely ineffective at treating advanced tumours, with long-term survival being very low. Molecularly-targeted inhibitors of protein kinases are effective in delaying progression of advanced renal tumours. These therapies revolve around inhibition of the vascular endothelial growth factor receptor tyrosine kinase and the mammalian target of rapamycin serine or threonine kinase signalling pathways. The genetic complexity of renal tumours revealed by gene-expression profiling and other molecular-genetic technologies indicate that inhibition of additional kinase-associated pathways could also prevent renal tumour growth. In this review, we discuss the use of molecularly-targeted kinase inhibitors in the treatment of renal-cell carcinoma and identify the next generation of kinase inhibitors that show promise for treatment.
Furge
Kyle A
KA
Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, MI, USA.
MacKeigan
Jeffrey P
JP
Teh
Bin T
BT
D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human