Author: Guillen-Ahlers, Hector

Source: Current Drug Targets, Volume 9, Number 7, July 2008 , pp. 591-600(10)

Publisher: Bentham Science Publishers

Abstract:

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.

Keywords: Wnt; renal cancer; frizzled related proteins; T cell factor-4; beta-catenin; von Hippel-Lindau; hypoxia-inducible protein-2

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138945008784911813

Publication date: 2008-07-01

More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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