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Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11717-22. doi: 10.1073/pnas.1120068109. Epub 2012 Jul 2.

Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors.

Author information

  • 1OncoMed Pharmaceuticals, Redwood City, CA 94063, USA. austin.gurney@oncomed.com

Abstract

The Wnt/β-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several coreceptors, has long been implicated in cancer. Here we demonstrate a therapeutic approach to targeting the Wnt pathway with a monoclonal antibody, OMP-18R5. This antibody, initially identified by binding to Frizzled 7, interacts with five Fzd receptors through a conserved epitope within the extracellular domain and blocks canonical Wnt signaling induced by multiple Wnt family members. In xenograft studies with minimally passaged human tumors, this antibody inhibits the growth of a range of tumor types, reduces tumor-initiating cell frequency, and exhibits synergistic activity with standard-of-care chemotherapeutic agents.

PMID:
22753465
[PubMed - indexed for MEDLINE]
PMCID:
PMC3406803
Free PMC Article

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