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|Ref Type||Journal Article|
|Authors||Gurney A, Axelrod F, Bond CJ, Cain J, Chartier C, Donigan L, Fischer M, Chaudhari A, Ji M, Kapoun AM, Lam A, Lazetic S, Ma S, Mitra S, Park IK, Pickell K, Sato A, Satyal S, Stroud M, Tran H, Yen WC, Lewicki J, Hoey T|
|Title||Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors.|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Date||2012 Jul 17|
|Abstract Text||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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Vantictumab||anti-Fzd7|OMP-18R5||WNT Inhibitor 10||Vantictumab (OMP-18R5) is a monoclonal antibody that targets Frizzled receptors 1, 2, 5, 7, and 8, resulting in decreased Wnt signaling and potentially leading to decreased tumor growth (PMID: 22753465, PMID: 31338636).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||lung non-small cell carcinoma||not applicable||Vantictumab||Preclinical - Pdx||Actionable||In a preclinical study, Vantictumab (OMP-18R5) inhibited tumor growth in 7/8 patient-derived xenograft models of non-small cell lung cancer (PMID: 22753465).||22753465|
|Unknown unknown||breast cancer||not applicable||Paclitaxel + Vantictumab||Preclinical - Pdx||Actionable||In a preclinical study, Vantictumab (OMP-18R5) worked synergistically with Taxol (paclitaxel) to inhibit tumor growth in patient-derived xenograft models of breast cancer (PMID: 22753465).||22753465|
|Unknown unknown||pancreatic cancer||not applicable||Gemcitabine + Vantictumab||Preclinical - Pdx||Actionable||In a preclinical study, Vantictumab (OMP-18R5) worked synergistically with Gemzar (gemcitabine) to inhibit tumor growth in patient-derived xenograft models of pancreatic cancer (PMID: 22753465).||22753465|
|APC wild-type CTNNB1 wild-type||colon cancer||predicted - sensitive||Vantictumab||Preclinical - Pdx||Actionable||In a preclinical study, Vantictumab (OMP-18R5) inhibited tumor growth in patient-derived xenograft models of colon cancer with wild-type CTNNB1 (beta-catenin) and APC (PMID: 22753465).||22753465|