vantictumab (OMP-18R5)

The most commonly used drugs, investigated in 3 or more clinical trials included DKN-01 [DKK1 neutralizing monoclonal antibody] (9.9%), PRI-724 [CBP/ β-catenin complex inhibitor] (4%), OMP-54F28 [Decoy Receptor for Wnt lignads] (4%), Vantictumab [monoclonal antibody against Frizzled receptors] (4%), Cirmtuzumab [monoclonal antibody against ROR1] (4%), and BHQ880 [monoclonal antibody against DKK1] (3%). Based on our analysis, we reckon that DKK1 is the most investigated Wnt pathway target in cancer clinical trials, with DKN-01 being the most explored drug. Out of the 91 studies, the highest number of trials were carried out in colorectal cancer, followed by multiple myeloma. The preponderance of the clinical trials in early phases and active status could be the possible reasons for the deficit of Wnt pathway modifiers for cancer therapy in clinical practice.

The combination of vantictumab and weekly paclitaxel was generally well tolerated with promising efficacy; however, the incidence of fractures limits future clinical development of this particular WNT inhibitor in metastatic breast cancer.

Knockdown of Fzd7 or using inhibitors of Wnt/Fzd (OMP-18R5/Vantictumad) decreased GC cell stemness, characterized as a decrease of spheroid formation ability and expression of stemness regulators...Furthermore, elevation of Myc expression rescued the effects of Fzd7 inhibition on GC cell stemness and chemoresistance. CONCLUSIONS Our results suggest that inhibition of Fzd7 decreases the stemness and chemotherapeutic resistance of GC cells.