Kinase targets in renal-cell carcinomas: reassessing the old and discovering the new

• Published in: The lancet oncology 2010-06, Vol.11 (6), p.571-578
• Main Authors: Furge, Kyle A, PhD, MacKeigan, Jeffrey P, PhD, Teh, Bin T, Dr
• Format: Article
• Language: English
• Subjects: Binding sites; Cancer therapies; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Cell Cycle Proteins - metabolism; Enzyme Activation; Hematology, Oncology and Palliative Medicine; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Kinases; Ligands; Mutation; Phosphatidylinositol 3-Kinases - metabolism; Protein Kinase Inhibitors - therapeutic use; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases - metabolism; Proteins; Radiation; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Vascular Endothelial Growth Factor - metabolism; Signal Transduction; TOR Serine-Threonine Kinases; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(09)70380-8

Summary 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.