Researchers have found that inhibiting the molecule Netrin-1 can diminish factors that contribute to the spread of cancer and its resistance to treatment. Preliminary human trials are promising, warranting further investigations into the wider implications and impact on patient survival rates.
The spread of cancer to different parts of the body, known as metastasis, along with resistance to chemotherapy, are the principal causes of treatment failure and mortality among cancer patients. The epithelial-mesenchymal transition (EMT) is a crucial biological process that allows cancer cells to disengage from surrounding cells and adopt invasive traits. EMT is instrumental in both the development of metastases and the development of resistance to existing cancer treatments. To date, no therapies specifically target EMT in cancer.
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Cutting-Edge Research on EMT Mechanisms
A publication in the esteemed journal Nature, spearheaded by Professor Cédric Blanpain of WEL Research Institute, director of the Stem Cells and Cancer Laboratory, and professor at the Free University of Brussels, demonstrated that Netrin-1, a molecule present in various cancer types, activates EMT in cancer cells. A drug designed to target Netrin-1 successfully inhibited EMT in these cells.
The team, including Justine Lengrand, Ievgenia Pastushenko, and Sebastiaan Vanuytven, identified that cancer cells undergoing EMT have elevated levels of Netrin-1 and its receptor UNC5B. Their research further indicated that increasing Netrin-1 levels encourages EMT, while inhibiting Netrin-1 effectively suppresses it.
Collaborative Efforts for a Potential Treatment
Working in partnership with NETRIS Pharma, which has formulated a therapeutic antibody that specifically blocks the Netrin-1 and UNC5B interaction, researchers from ULB demonstrated that administering this antibody not only lessened tumor formation but also inhibited EMT within these tumors. This, in turn, limited their metastatic potential and made them more susceptible to chemotherapy. “We are exceptionally pleased to have identified the inaugural drug that can in vivo target EMT, thereby mitigating the occurrence of metastases and resistance to chemotherapy,” stated Justine Lengrand, the study’s primary author.
After validating the efficacy of the anti-Netrin-1 antibody in animal models, ULB researchers collaborated with colleagues from the University of Lyon and Nétris Pharma to assess the drug’s impact on EMT in patients with endometrial cancers.
Clinical Investigations and Future Directions
In clinical trials conducted in France, the anti-Netrin-1 antibody was administered to patients and exhibited no toxicity while being well-tolerated. Biopsies taken before and after drug administration indicated that the therapy effectively reduced EMT in endometrial cancer patients.
“This is a landmark achievement. We have identified a new medication that can diminish EMT, reduce metastatic spread, and enhance responsiveness to chemotherapy in preclinical models,” commented Professor Cédric Blanpain, the project lead. “We aim to ascertain whether administering the anti-Netrin-1 antibody and the resultant reduction in EMT will translate to improved clinical outcomes in cancer treatment, including chemotherapy and immunotherapy.”
The collaboration between Belgian and French researchers has brought forth innovative therapeutic strategies that could potentially make tumors more receptive to chemotherapy and impede both tumor progression and resistance to existing cancer treatments. “Long-term studies will be required to evaluate this new therapy’s impact on the survival rates of patients with endometrial cancers and to test its efficacy against other cancers that also display EMT, such as lung or breast cancers,” added Professor Cédric Blanpain, the study’s concluding author.
Reference
The study, titled “Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer,” was published in Nature on 2 August 2023. DOI: 10.1038/s41586-023-06367-z.
This research was facilitated through the support of various organizations including FNRS, TELEVIE, WEL Research Institute, the Fondation Contre le Cancer, the ULB Foundation, the foundation Julie et Francoise Drion, the Fond Erasme, FNRS/FWO EOS, and the European Research Council (ERC).
Frequently Asked Questions (FAQs) about Netrin-1 Inhibition in Cancer Treatment
What is the main finding of the research study?
The primary discovery of the research is that inhibiting the molecule Netrin-1 can significantly reduce factors contributing to cancer metastasis and resistance to chemotherapy. This has been substantiated by early human trials which have shown promise.
What is Netrin-1 and its role in cancer?
Netrin-1 is a molecule expressed by tumor cells in various types of cancers. It has been found to stimulate the Epithelial-Mesenchymal Transition (EMT) in tumor cells. EMT is a key biological process that allows cancer cells to detach from neighboring cells and acquire invasive properties.
What is Epithelial-Mesenchymal Transition (EMT)?
Epithelial-Mesenchymal Transition (EMT) is a biological process that allows cells to switch from an epithelial state to a mesenchymal state. This transition enables cancer cells to disengage from their neighboring cells, acquire invasive traits, and contributes to the development of metastases and resistance to cancer therapies.
Who led the research?
The research was led by Professor Cédric Blanpain, who is an investigator at the WEL Research Institute, director of the Stem Cells and Cancer Laboratory, and a professor at the Free University of Brussels.
What organizations supported the research?
The research received support from multiple organizations, including FNRS, TELEVIE, WEL Research Institute, the Fondation Contre le Cancer, the ULB Foundation, the foundation Julie et Francoise Drion, the Fond Erasme, FNRS/FWO EOS, and the European Research Council (ERC).
Are there any clinical trials related to this research?
Yes, clinical trials have been conducted in France, administering the anti-Netrin-1 antibody to patients. The trials showed that the therapy was well-tolerated, exhibited no toxicity, and effectively reduced EMT in patients with endometrial cancers.
What are the future prospects of this research?
The future work aims to assess whether the administration of the anti-Netrin-1 antibody and the resultant reduction in EMT will improve clinical responses to chemotherapy and immunotherapy. Long-term studies are also needed to evaluate the therapy’s impact on the survival rates of patients and its efficacy against other types of cancers that display EMT.
Where was the research published?
The research was published in the esteemed scientific journal Nature on 2 August 2023. The DOI is 10.1038/s41586-023-06367-z.
More about Netrin-1 Inhibition in Cancer Treatment
- Nature Journal Article
- WEL Research Institute
- Free University of Brussels
- European Research Council (ERC)
- Fondation Contre le Cancer
- FNRS
- TELEVIE
- ULB Foundation
- Fond Erasme
7 comments
This is promising but I wonder how far we are from actually using this in day-to-day treatment. Research is one thing, practical application is another.
Wow, this is really groundbreaking stuff! Finally, we’ve got something that could potentially target metastasis. Hope this moves from trials to treatment asap.
Intriguing! If they really manage to move this into practical medicine, this could be a game changer for cancer treatment. Fingers crossed.
Finally, some hope in the grim world of cancer research. Wonder how fast they can get this out to the public. We need it like yesterday.
A bit hard to digest all the scientific jargon, but if this is as big as it sounds then hats off to the researchers. Netrin-1 might just become a household name.
so what’s the catch? Every time I hear about a ‘breakthrough’, there always seems to be some kind of downside not discussed.
Sounds like a long road ahead but it’s a start. Anyone know if this applies to all types of cancer or just some?