Reference Detail

Ref Type Journal Article
PMID (22753465)
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
Vol 109
Issue 29
Date 2012 Jul 17
URL
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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Vantictumab Vantictumab 2 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Vantictumab anti-Fzd7|OMP-18R5 WNT Inhibitor 9 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).
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
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
Unknown unknown non-small cell lung 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 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
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