Unlocking the Wnt pathway: therapeutic potential of selective targeting FZD7 in cancer

The Wnt signaling is of paramount pathophysiological importance. Despite showing promising anticancer activities in pre-clinical studies, current Wnt pathway inhibitors face complications in clinical trials resulting from on-target toxicity. Hence, the targeting of pathway component(s) that are essential for cancer but dispensable for normal physiology is key to the development of a safe Wnt signaling inhibitor. Frizzled7 (FZD7) is a Wnt pathway receptor that is redundant in healthy tissues but crucial in various cancers. FZD7 modulates diverse aspects of carcinogenesis, including cancer growth, metastasis, maintenance of cancer stem cells, and chemoresistance. In this review, we describe state-of-the-art knowledge of the functions of FZD7 in carcinogenesis and adult tissue homeostasis. Next, we overview the development of small molecules and biomolecules that target FZD7. Finally, we discuss challenges and possibilities in developing FZD7-selective antagonists