title: 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 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.
authors: OncoMed Pharmaceuticals, Redwood City, CA 94063, USA. austin.gurney@oncomed.com
authors: Austin
authors: A
authors: Gurney
authors: Fumiko
authors: F
authors: Axelrod
authors: Christopher J
authors: CJ
authors: Bond
authors: Jennifer
authors: J
authors: Cain
authors: Cecile
authors: C
authors: Chartier
authors: Lucas
authors: L
authors: Donigan
authors: Marcus
authors: M
authors: Fischer
authors: Aurélie
authors: A
authors: Chaudhari
authors: May
authors: M
authors: Ji
authors: Ann M
authors: AM
authors: Kapoun
authors: Andrew
authors: A
authors: Lam
authors: Sasha
authors: S
authors: Lazetic
authors: Shirley
authors: S
authors: Ma
authors: Satyajit
authors: S
authors: Mitra
authors: In-Kyung
authors: IK
authors: Park
authors: Kellie
authors: K
authors: Pickell
authors: Aaron
authors: A
authors: Sato
authors: Sanjeev
authors: S
authors: Satyal
authors: Michelle
authors: M
authors: Stroud
authors: Hoang
authors: H
authors: Tran
authors: Wan-Ching
authors: WC
authors: Yen
authors: John
authors: J
authors: Lewicki
authors: Timothy
authors: T
authors: Hoey
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004357:Drug Synergism; D051157:Frizzled Receptors / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics; D007150:Immunohistochemistry; D016086:Lentivirus; D008156:Luciferases; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019151:Peptide Library; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051157:Frizzled Receptors; D007140:Immunoglobulin Fab Fragments; D019151:Peptide Library; D008156:Luciferases