WNT5A as a therapeutic target in breast cancer

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...

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Autores principales: Prasad, Chandra Prakash, Manchanda, Mansi, Mohapatra, Purusottam, Andersson, Tommy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510844/
https://www.ncbi.nlm.nih.gov/pubmed/30171384
http://dx.doi.org/10.1007/s10555-018-9760-y
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author Prasad, Chandra Prakash
Manchanda, Mansi
Mohapatra, Purusottam
Andersson, Tommy
author_facet Prasad, Chandra Prakash
Manchanda, Mansi
Mohapatra, Purusottam
Andersson, Tommy
author_sort Prasad, Chandra Prakash
collection PubMed
description 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.
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spelling pubmed-65108442019-05-28 WNT5A as a therapeutic target in breast cancer Prasad, Chandra Prakash Manchanda, Mansi Mohapatra, Purusottam Andersson, Tommy Cancer Metastasis Rev Non-Thematic Review 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. Springer US 2018-08-31 2018 /pmc/articles/PMC6510844/ /pubmed/30171384 http://dx.doi.org/10.1007/s10555-018-9760-y Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Non-Thematic Review
Prasad, Chandra Prakash
Manchanda, Mansi
Mohapatra, Purusottam
Andersson, Tommy
WNT5A as a therapeutic target in breast cancer
title WNT5A as a therapeutic target in breast cancer
title_full WNT5A as a therapeutic target in breast cancer
title_fullStr WNT5A as a therapeutic target in breast cancer
title_full_unstemmed WNT5A as a therapeutic target in breast cancer
title_short WNT5A as a therapeutic target in breast cancer
title_sort wnt5a as a therapeutic target in breast cancer
topic Non-Thematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510844/
https://www.ncbi.nlm.nih.gov/pubmed/30171384
http://dx.doi.org/10.1007/s10555-018-9760-y
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