Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs.


Journal Article (Review)

Wnt signaling is dysregulated in many cancers and is therefore an attractive therapeutic target. The focus of drug development has recently shifted away from downstream inhibitors of β-catenin. Active inhibitors of Wnt secretion and Wnt/receptor interactions have been developed that are now entering clinical trials. Such agents include inhibitors of Wnt secretion, as well as recombinant proteins that minimize Wnt-Frizzled interactions. These new therapies arrive together with the recent insight that cancer-specific upregulation of Wnt receptors at the cell surface regulates cellular sensitivity to Wnts. Loss-of-function mutations in RNF43 or ZNRF3 and gain-of-function chromosome translocations involving RSPO2 and RSPO3 are surprisingly common and markedly increase Wnt/β-catenin signaling in response to secreted Wnts. These mutations may be predictive biomarkers to select patients responsive to newly developed upstream Wnt inhibitors.

Full Text

Duke Authors

Cited Authors

  • Madan, B; Virshup, DM

Published Date

  • May 2015

Published In

Volume / Issue

  • 14 / 5

Start / End Page

  • 1087 - 1094

PubMed ID

  • 25901018

Pubmed Central ID

  • 25901018

Electronic International Standard Serial Number (EISSN)

  • 1538-8514

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-14-1038


  • eng

Conference Location

  • United States