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WNT5A as a therapeutic target in breast cancer

Prasad, Chandra Prakash LU ; Manchanda, Mansi LU ; Mohapatra, Purusottam LU and Andersson, Tommy LU (2018) In Cancer and Metastasis Reviews p.1-12
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Breast cancer, Cell migration and invasion, Foxy5, Metastasis, WNT5A
in
Cancer and Metastasis Reviews
pages
1 - 12
publisher
Springer
external identifiers
  • scopus:85052787279
ISSN
0167-7659
DOI
10.1007/s10555-018-9760-y
language
English
LU publication?
yes
id
62ff96d4-239d-4eb1-b404-71dd38bc4a15
date added to LUP
2018-09-28 12:10:10
date last changed
2019-03-31 05:01:54
@article{62ff96d4-239d-4eb1-b404-71dd38bc4a15,
  abstract     = {<p>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.</p>},
  author       = {Prasad, Chandra Prakash and Manchanda, Mansi and Mohapatra, Purusottam and Andersson, Tommy},
  issn         = {0167-7659},
  keyword      = {Breast cancer,Cell migration and invasion,Foxy5,Metastasis,WNT5A},
  language     = {eng},
  month        = {08},
  pages        = {1--12},
  publisher    = {Springer},
  series       = {Cancer and Metastasis Reviews},
  title        = {WNT5A as a therapeutic target in breast cancer},
  url          = {http://dx.doi.org/10.1007/s10555-018-9760-y},
  year         = {2018},
}