A Second WNT for Old Drugs: Drug Repositioning against WNT-Dependent Cancers.

Cancers (Basel)

Department of Pharmacology and Toxicology, University of Lausanne, Lausanne 1011, Switzerland.

Published: July 2016

Aberrant WNT signaling underlies cancerous transformation and growth in many tissues, such as the colon, breast, liver, and others. Downregulation of the WNT pathway is a desired mode of development of targeted therapies against these cancers. Despite the urgent need, no WNT signaling-directed drugs currently exist, and only very few candidates have reached early phase clinical trials. Among different strategies to develop WNT-targeting anti-cancer therapies, repositioning of existing drugs previously approved for other diseases is a promising approach. Nonsteroidal anti-inflammatory drugs like aspirin, the anti-leprotic clofazimine, and the anti-trypanosomal suramin are among examples of drugs having recently revealed WNT-targeting activities. In total, 16 human-use drug compounds have been found to be working through the WNT pathway and show promise for their prospective repositioning against various cancers. Advances, hurdles, and prospects of developing these molecules as potential drugs against WNT-dependent cancers, as well as approaches for discovering new ones for repositioning, are the foci of the current review.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963808PMC
http://dx.doi.org/10.3390/cancers8070066DOI Listing

Publication Analysis

Top Keywords

wnt-dependent cancers
8
wnt pathway
8
drugs
6
second wnt
4
wnt drugs
4
drugs drug
4
repositioning
4
drug repositioning
4
repositioning wnt-dependent
4
cancers
4

Similar Publications

P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker.

Oncogenesis

November 2024

Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China.

Glioblastoma stem cells (GSCs) are pivotal in the recurrence and drug resistance of glioblastoma multiforme (GBM). However, precision therapeutic and diagnostic markers for GSCs have not been fully established. Here, using bioinformatics and experimental analysis, we identified P4HB, a protein disulfide isomerase, as a serum marker that maintains stemness in GSCs through the Wnt/β-catenin signaling pathway.

View Article and Find Full Text PDF

RNF43 and ZNRF3: Versatile regulators at the membrane and their role in cancer.

Biochim Biophys Acta Rev Cancer

November 2024

Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, the Netherlands.. Electronic address:

RNF43 and ZNRF3 are recognized as important regulators of Wnt/β-catenin signaling by maintaining Wnt-receptors at minimal essential levels. In various cancer types, particularly gastrointestinal tumors, mutations in these genes lead to abnormal Wnt-dependent activation of β-catenin signaling. However, recent findings implicate RNF43/ZNRF3 also in the regulation of other tumor-related proteins, including EGFR, BRAF, and the BMP-signaling pathway, which may have important implications for tumor biology.

View Article and Find Full Text PDF

Emerging therapeutic strategies for Wnt-dependent colon cancer targeting macropinocytosis.

Cells Dev

December 2024

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Binghamton, Binghamton, NY, USA.

Aberrations in the Wnt signaling pathway, particularly mutations in genes like APC and β-catenin, are pivotal in initiating and driving the progression of colorectal cancer (CRC), establishing this pathway as a crucial target for therapeutic intervention. Membrane trafficking plays a key role in regulating Wnt signaling by controlling the activation, modulation, and secretion of essential signaling molecules that contribute to CRC progression. This review explores the connection between membrane trafficking and Wnt signaling, with a specific focus on macropinocytosis-an endocytic process involved in nutrient uptake that also plays a role in Wnt signal regulation.

View Article and Find Full Text PDF

Development of -(4-(1-Imidazol-1-yl)phenyl)-4-chlorobenzenesulfonamide, a Novel Potent Inhibitor of β-Catenin with Enhanced Antitumor Activity and Metabolic Stability.

J Med Chem

November 2024

Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185 Rome, Italy.

The potential as a cancer therapeutic target of the recently reported hotspot binding region close to Lys508 of the β-catenin armadillo repeat domain was not exhaustively explored. In order to get more insight, we synthesized novel -(heterocyclylphenyl)benzenesulfonamides -. The new compounds significantly inhibited Wnt-dependent transcription as well as SW480 and HCT116 cancer cell proliferation.

View Article and Find Full Text PDF

Wnt signaling in the tumor microenvironment: A driver of brain tumor dynamics.

Life Sci

December 2024

Laboratory of Veterinary Biochemistry, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju 63243, South Korea; Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, South Korea. Electronic address:

The Wnt signaling pathway is important for cell growth and development in the central nervous system and its associated vasculature. Thus, it is an interesting factor for establishing anti-brain cancer therapy. However, simply inhibiting the Wnt signaling pathway in patients with brain tumors is not an effective anti-cancer therapy.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!