TY - EJOU AU - Sun, Yu AU - Wang, Wei AU - Zhao, Chenghai TI - Frizzled Receptors in Tumors, Focusing on Signaling, Roles, Modulation Mechanisms, and Targeted Therapies T2 - Oncology Research PY - 2020 VL - 28 IS - 6 SN - 1555-3906 AB - Wnt molecules play crucial roles in development and adult homeostasis through their receptors Frizzled proteins (Fzds). Fzds mediate canonical b-catenin pathway and various noncanonical b-catenin-independent pathways. Aberrant Fzd signaling is involved in many diseases including cancer. Wnt/b-catenin is a well-established oncogenic pathway involved in almost every aspect of tumor development. However, Fzd-mediated noncanonical Wnt pathways function as both tumor promoters and tumor suppressors depending on cellular context. Fzd-targeted therapies have proven to be effective on cultured tumor cells, tumor cell xenografts, mouse tumor models, and patient-derived xenografts (PDX). Moreover, Fzd-targeted therapies synergize with chemotherapy in preclinical models. However, the occurrence of fragility fractures in patients treated with Fzd-targeted agents such as OMP- 54F28 and OMP-18R5 limits the development of this combination. Along with new insights on signaling, roles, and modulation mechanisms of Fzds in human tumors, more Fzd-related therapeutic targets will be developed. KW - Wnt; Frizzled; β-Catenin; Tumor DO - 10.3727/096504020X16014648664459