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Cancers
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Advances in Targeting Wnt Signaling in Cancer
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Advances in Targeting Wnt Signaling in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 6956

Special Issue Editors

Dr. Dustin Flanagan

E-Mail Website
Guest Editor
Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK
Interests: Wnt signalling; stem cells; gastric cancer; colon cancer
Dr. Arafath K. Najumudeen

E-Mail Website
Guest Editor
Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK
Interests: colon cancer; Ras signalling; stem cells; metabolism

Special Issue Information

Dear Colleagues,

This Special Issue will delve into the recent advances made in targeting the Wnt pathway to treat various cancer types. Given the ubiquitous requirement of Wnt signalling for cancer initiation and progression, but also stem cell maintenance in multiple tissue types, we will pay close attention to the benefits and potential side effects of targeting this pathway.

This Special Issue could include original research articles, reviews, opinions from experts in the field, and cover a broad range of topics including molecular mechanisms and novel regulators of Wnt signalling, the role of Wnt signalling in stem cells and cancer, new tools to study Wnt signalling dynamics, targeting the tumour microenvironment via Wnt, drug discovery and so on.

We hope this Special Issue will provide insight and answers for unresolved questions and gaps in the field surrounding the Wnt pathway and how we can translate current basic research findings into improved clinical outcomes.

We look forward to receiving your contributions.

Dr. Dustin Flanagan
Dr. Arafath K. Najumudeen
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Wnt signalling
  • frizzled
  • cancer
  • stem cells
  • tumour microenvironment
  • β-catenin/TCF
  • destruction complex
  • non-canonical signalling
  • Wnt-targeted therapeutics

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (2 papers)

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13 pages, 3098 KiB  
Communication
The FDA-Approved Drug Pyrvinium Selectively Targets ER+ Breast Cancer Cells with High INPP4B Expression
by Samuel J. Rodgers, Lisa M. Ooms and Christina A. Mitchell
Cancers 2023, 15(1), 135; https://doi.org/10.3390/cancers15010135 - 26 Dec 2022
Cited by 6 | Viewed by 2213
Abstract
The majority of breast cancers are estrogen receptor-positive (ER+), and endocrine therapies that suppress ER signaling are the standard-of-care treatment for this subset. However, up to half of all ER+ cancers eventually relapse, highlighting a need for improved clinical therapies. [...] Read more.
The majority of breast cancers are estrogen receptor-positive (ER+), and endocrine therapies that suppress ER signaling are the standard-of-care treatment for this subset. However, up to half of all ER+ cancers eventually relapse, highlighting a need for improved clinical therapies. The phosphoinositide phosphatase, INPP4B, is overexpressed in almost half of all ER+ breast cancers, and promotes Wnt/β-catenin signaling, cell proliferation and tumor growth. Here, using cell viability assays, we report that INPP4B overexpression does not affect the sensitivity of ER+ breast cancer cells to standard-of-care treatments including the anti-estrogen 4-hydroxytamoxifen (4-OHT) or the PI3Kα inhibitor alpelisib. Examination of four small molecule Wnt inhibitors revealed that ER+ breast cancer cells with INPP4B overexpression were more sensitive to the FDA-approved drug pyrvinium and a 4-OHT-pyrvinium combination treatment. Using 3D culture models, we demonstrated that pyrvinium selectively reduced the size of INPP4B-overexpressing ER+ breast cancer spheroids in the presence and absence of 4-OHT. These findings suggest that repurposing pyrvinium as a Wnt inhibitor may be an effective therapeutic strategy for human ER+ breast cancers with high INPP4B levels. Full article
(This article belongs to the Special Issue Advances in Targeting Wnt Signaling in Cancer)
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Review

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23 pages, 2948 KiB  
Review
Therapeutic Potential of Naturally Occurring Small Molecules to Target the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer
by Luiz F. S. Oliveira, Danilo Predes, Helena L. Borges and Jose G. Abreu
Cancers 2022, 14(2), 403; https://doi.org/10.3390/cancers14020403 - 14 Jan 2022
Cited by 22 | Viewed by 3823
Abstract
Colorectal cancer (CRC) ranks second in the number of cancer deaths worldwide, mainly due to late diagnoses, which restrict treatment in the potentially curable stages and decrease patient survival. The treatment of CRC involves surgery to remove the tumor tissue, in addition to [...] Read more.
Colorectal cancer (CRC) ranks second in the number of cancer deaths worldwide, mainly due to late diagnoses, which restrict treatment in the potentially curable stages and decrease patient survival. The treatment of CRC involves surgery to remove the tumor tissue, in addition to radiotherapy and systemic chemotherapy sessions. However, almost half of patients are resistant to these treatments, especially in metastatic cases, where the 5-year survival rate is only 12%. This factor may be related to the intratumoral heterogeneity, tumor microenvironment (TME), and the presence of cancer stem cells (CSCs), which is impossible to resolve with the standard approaches currently available in clinical practice. CSCs are APC-deficient, and the search for alternative therapeutic agents such as small molecules from natural sources is a promising strategy, as these substances have several antitumor properties. Many of those interfere with the regulation of signaling pathways at the central core of CRC development, such as the Wnt/β-catenin, which plays a crucial role in the cell proliferation and stemness in the tumor. This review will discuss the use of naturally occurring small molecules inhibiting the Wnt/β-catenin pathway in experimental CRC models over the past decade, highlighting the molecular targets in the Wnt/β-catenin pathway and the mechanisms through which these molecules perform their antitumor activities. Full article
(This article belongs to the Special Issue Advances in Targeting Wnt Signaling in Cancer)
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