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

Yonika Larasati1, Cédric Boudou1, Alexey Koval1

  • 1Department of Cell Physiology and Metabolism, Translational Research Centre in Oncohaematology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.

Drug Discovery Today
|December 16, 2021
PubMed

Insights

Targeting Frizzled7 (FZD7) offers a promising strategy for cancer therapy by inhibiting Wnt signaling. This receptor is crucial for cancer but less vital in healthy tissues, potentially reducing toxicity from inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Wnt signaling plays a critical role in pathophysiological processes.
  • Current Wnt pathway inhibitors exhibit on-target toxicity, limiting clinical efficacy.
  • Identifying cancer-specific targets within the Wnt pathway is essential for developing safer therapeutics.

Purpose of the Study:

  • To review the functions of Frizzled7 (FZD7) in cancer and normal tissue homeostasis.
  • To summarize the development of FZD7-targeting agents.
  • To discuss the challenges and opportunities for FZD7-selective antagonists.

Main Methods:

  • Literature review of FZD7's role in carcinogenesis and tissue homeostasis.
  • Overview of small molecule and biomolecule development targeting FZD7.
  • Analysis of challenges and future directions for FZD7 antagonists.

Main Results:

  • FZD7 is crucial for cancer growth, metastasis, cancer stem cell maintenance, and chemoresistance.
  • FZD7 is redundant in healthy tissues, suggesting it's a viable cancer-specific target.
  • Various small molecules and biomolecules targeting FZD7 have been developed.

Conclusions:

  • FZD7 represents a key target for developing Wnt signaling inhibitors with improved safety profiles.
  • Targeting FZD7 holds potential for effective cancer treatment by exploiting its cancer-specific essentiality.
  • Further research into FZD7-selective antagonists is warranted to overcome clinical challenges.

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