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Updated: Feb 5, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
WNT5A as a therapeutic target in breast cancer
Chandra Prakash Prasad1,2, Mansi Manchanda1, Purusottam Mohapatra1
1Cell and Experimental Pathology, Department of Translational Medicine, Lund University, CRC, Malmö, Sweden.
Abstract:
Despite the clinical development of novel adjuvant and neoadjuvant chemotherapeutic drugs, metastatic breast cancer is one of the leading causes of cancer-related death among women. The present review focuses on the relevance, mechanisms, and therapeutic potential of targeting WNT5A as a future anti-metastatic treatment strategy for breast cancer patients by restoring WNT5A signaling as an innovative therapeutic option. WNT5A is an auto- and paracrine β-catenin-independent ligand that has been shown to induce tumor suppression as well as oncogenic signaling, depending upon cancer type. In breast cancer patients, WNT5A protein expression has been observed to be significantly reduced in between 45 and 75% of the cases and associated with early relapse and reduced disease-free survival. WNT5A triggers various downstream signaling pathways in breast cancer that primarily affect tumor cell migration and invasion. The accumulated in vitro results reveal that treatment of WNT5A-negative breast cancer cells with recombinant WNT5A caused different tumor-suppressive responses and in particular it impaired migration and invasion. The anti-migratory/invasive and anti-metastatic effects of reconstituting WNT5A signaling by the small WNT5A mimicking peptide Foxy5 form the basis for two successful clinical phase 1-studies aiming at determining safety and pharmacokinetics as well as defining dose-level for a subsequent phase 2-study. We conclude that re-installation of WNT5A signaling is an attractive and promising anti-metastatic therapeutic approach for future treatment of WNT5A-negative breast cancer patients.
Insights
Restoring WNT5A signaling, often lost in breast cancer, shows promise in preventing metastasis. Clinical studies with the WNT5A-mimicking peptide Foxy5 are exploring this innovative anti-cancer treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Metastatic breast cancer remains a significant cause of cancer-related mortality despite advances in chemotherapy.
- WNT5A signaling plays a complex role in cancer, acting as a tumor suppressor or promoter depending on the context.
- Reduced WNT5A expression in breast cancer correlates with increased risk of relapse and poorer survival rates.
Purpose of the Study:
- To review the significance, mechanisms, and therapeutic potential of targeting WNT5A signaling in breast cancer.
- To explore the restoration of WNT5A signaling as a novel anti-metastatic treatment strategy.
- To evaluate the efficacy of WNT5A re-instillation for WNT5A-negative breast cancer patients.
Main Methods:
- Review of existing literature on WNT5A's role in breast cancer.
- Analysis of in vitro studies demonstrating WNT5A's effect on tumor cell migration and invasion.
- Consideration of clinical phase 1 studies evaluating the WNT5A-mimicking peptide Foxy5.
Main Results:
- WNT5A protein expression is significantly reduced in 45-75% of breast cancer cases.
- Recombinant WNT5A treatment of WNT5A-negative cells impaired migration and invasion, indicating tumor-suppressive effects.
- The WNT5A-mimicking peptide Foxy5 demonstrated anti-migratory, anti-invasive, and anti-metastatic effects in preclinical models.
Conclusions:
- Restoring WNT5A signaling is a promising therapeutic strategy for combating breast cancer metastasis.
- The peptide Foxy5 shows potential for clinical application in treating WNT5A-negative breast cancer.
- Targeting WNT5A represents an innovative approach to improve outcomes for breast cancer patients.
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