2012
DOI: 10.1073/pnas.1120068109
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Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors

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 min… Show more

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Cited by 497 publications
(452 citation statements)
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“…Examples include anti-LRP6 antibodies (18), and the anti-Frizzled antibody vantictumab (OMP-18R5; ref. 19). Vantictumab binds to 5 of the 10 Fzd receptors recognizing an epitope spanning the "cleft" region of Fzd that contains highly conserved residues (19,20).…”
Section: Upstream Inhibitors Of Wnt Production and Functionmentioning
confidence: 99%
See 2 more Smart Citations
“…Examples include anti-LRP6 antibodies (18), and the anti-Frizzled antibody vantictumab (OMP-18R5; ref. 19). Vantictumab binds to 5 of the 10 Fzd receptors recognizing an epitope spanning the "cleft" region of Fzd that contains highly conserved residues (19,20).…”
Section: Upstream Inhibitors Of Wnt Production and Functionmentioning
confidence: 99%
“…19). Vantictumab binds to 5 of the 10 Fzd receptors recognizing an epitope spanning the "cleft" region of Fzd that contains highly conserved residues (19,20). Vantictumab may effectively target a subset of cancers that are dependent on the function of the appropriate Fzds.…”
Section: Upstream Inhibitors Of Wnt Production and Functionmentioning
confidence: 99%
See 1 more Smart Citation
“…Another group showed indomethacin and aspirin induced reduced expression of β-catenin/TCF responsive genes, with no significant effect on nuclear localization of β-catenin (Dihlmann et al, 2001). In another study, it was shown a monoclonal antibody against frizzled receptor, OMP-18R5, inhibited tumor growth in xenograft models of several human tumors including pancreatic, breast, and lung cancer and decreased tumor-initiating cell frequency (Gurney et al, 2012). Table 2 summarizes a list of inhibitors of self-renewal pathways, some of which are already used in the clinic.…”
Section: F I G U Re 2 S I G N a L Tr A N S D U C T I O N P A T H W mentioning
confidence: 99%
“…The second class including the Dkk family exerts inhibition by endocytosis of co-receptors LRP5/6 (Kawano et al, 2003). Several Wnt antagonists, including Frzb/sFRP3 and Dkk-3, function as tumor suppressors (Zi et al, 2005;Guo et al, 2008;Abarzua et al, 2005;Rubin et al, 2010;Gurney et al, 2012). WIF-1 is a unique Wnt antagonist, structurally distinct from sFRP and Dkk families, which contains a WIF domain for Wnt binding activity and epidermal growth factor (EGF) repeats (Hsieh et al, 1999).…”
Section: The Wnt/catenin Pathway Is Very Important In Osamentioning
confidence: 99%