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Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors

Nithya Krishnamurthy1, Razelle Kurzrock2

  • 1Center for Personalized Cancer Therapy, UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.

Cancer Treatment Reviews
|November 24, 2017
PubMed

Insights

The Wnt signaling pathway regulates stem cells and organ development. Aberrant Wnt activation drives cancers, posing therapeutic challenges due to its role in normal tissue repair.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The Wnt/beta-catenin pathway is crucial for cellular functions like stem cell regeneration and organogenesis.
  • It involves canonical (beta-catenin dependent) and non-canonical (beta-catenin independent) signaling cascades.
  • Wnt pathway dysregulation is linked to colorectal, breast, lung, and hematopoietic cancers, often associated with tumor suppressor gene mutations (e.g., APC).

Purpose of the Study:

  • To comprehensively review the Wnt pathway's role in cellular functions and cancer.
  • To explore the interactions between Wnt, Notch, and Sonic Hedgehog pathways.
  • To discuss current therapeutic strategies and challenges targeting Wnt signaling in malignancies.

Main Methods:

  • Literature review of Wnt pathway signaling.
  • Analysis of Wnt pathway crosstalk with Notch and Sonic Hedgehog pathways.
  • Summary of current effectors, inhibitors, and clinical trial updates for Wnt-targeted cancer therapies.

Main Results:

  • Wnt pathway activation is critical for intestinal stem cell maintenance but its dysregulation contributes to various cancers.
  • The Wnt pathway interacts with Notch and Sonic Hedgehog pathways, influencing cancer development and treatment.
  • Significant challenges exist in developing Wnt inhibitors that are effective against cancer without compromising normal stem cell function.

Conclusions:

  • The Wnt pathway is a key player in both normal development and oncogenesis.
  • Understanding Wnt pathway crosstalk is vital for effective cancer therapeutic interventions.
  • Further research is needed to develop targeted therapies for Wnt-driven cancers with minimal side effects on somatic stem cells.
Keywords:
Beta-cateninColorectal cancersGamma secretaseHedgehogTargeted therapyWnt

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