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Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
Targeting the Wnt signalling pathway in cancer: prospects and perils
Holly V Shaw1, Alexey Koval2, Vladimir L Katanaev3
1Department of Cell Physiology and Metabolism, Translational Research Centre in Oncohaematology, Faculty of Medicine, University of Geneva, Switzerland / Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Switzerland.
Abstract:
The Wnt pathway, involved in cancer development and progression, has for a long time been said to be undruggable, owing to its complexity and involvement in stem cell biology. This mindset has shifted in the last few years as new research and insights into the pathway mechanisms specific to tumour cells become apparent, leading to the development of multiple compounds targeting the pathway. In this review, we introduce the Wnt pathway and its connections to cancer biology and therapy resistance. We further dive into the details of drugs that have entered clinical trials, examining their successes and side effects. We show that these drugs all have one thing in common: in order to be successful, the drugs must target tumour specific activated sub-branches of the pathway, either at the receptor level or at the nuclear transcription level.
Insights
The Wnt pathway, once deemed undruggable, is now a target for cancer therapies. New drugs focus on tumor-specific Wnt pathway branches for improved efficacy and reduced side effects in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- The Wnt pathway is implicated in cancer development, progression, and therapy resistance.
- Its complexity and role in stem cell biology historically made it a challenging therapeutic target.
- Recent advancements have revealed tumor-specific Wnt pathway mechanisms, enabling targeted drug development.
Purpose of the Study:
- To review the Wnt pathway's role in cancer biology and therapy resistance.
- To introduce and examine drugs targeting the Wnt pathway that have entered clinical trials.
- To identify common principles for successful Wnt-targeted cancer therapies.
Main Methods:
- Literature review of Wnt pathway research in cancer.
- Analysis of clinical trial data for Wnt-targeting drugs.
- Examination of drug mechanisms, successes, and side effects.
Main Results:
- Multiple compounds targeting the Wnt pathway are now in clinical trials.
- Successful Wnt-targeting drugs must inhibit tumor-specific activated sub-branches.
- Targeting can occur at the receptor or nuclear transcription levels.
Conclusions:
- The Wnt pathway is becoming a druggable target in oncology.
- Therapeutic success relies on precision targeting of tumor-specific Wnt pathway activations.
- Further research into Wnt pathway modulation holds promise for cancer treatment.
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