Wnt signaling in renal cancer.
About one fourth of people diagnosed with kidney cancer in 2007, are expected to die of this disease within 5 years from the date of diagnosis. Recent years have produced novel drugs, some with FDA approval, and many in clinical trials, all showing very discrete results. Failure in finding effective treatments to improve survival with drugs mainly targeting VEGF and its downstream effectors, urges to shift the drug development targets to other unexploited pathways shown to be also involved in renal cancer. Several studies show alterations in the Wnt signaling pathway, many of which differ from those implicated in other human cancers. Unlike colorectal or hepatocellular carcinomas, where APC and axin mutations, respectively, are the main Wnt signaling deregulating event, renal carcinomas seem to be affected by other factors. Recent studies have presented VHL, a tumor suppressor gene strongly associated with renal cell carcinoma, as a beta-catenin target. This confirms that Wnt signaling is likely playing a central role during renal carcinoma development, which needs to be considered and addressed to treat this disease. This review outlines briefly the molecular biology of the most common renal cancers and the drug treatments currently used to treat the disease. The canonical Wnt pathway is reviewed more carefully adding specific features in a renal carcinoma context, which present potential targets for drug development and biomarker use.
Guillén-Ahlers
Héctor
H
W.M. Keck Center for Transgene Research, Department of Chemistry and Biochemistry, University of Notre Dame, USA. hguillen@nd.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D015996:Survival Rate; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D000970:Antineoplastic Agents; D051153:Wnt Proteins; D051176:beta Catenin; D051794:Von Hippel-Lindau Tumor Suppressor Protein