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From discovery to mechanism — and beyond
NEW PUBLICATION · 2026
NEW PUBLICATION · 2026
A combinatorial EV-miRNA signature mediates the anti-tumoral activity of NFAT3-regulated extracellular vesicles in aggressive cancers
A combinatorial EV-miRNA signature mediates the anti-tumoral activity of NFAT3-regulated extracellular vesicles in aggressive cancers
Molecular Therapy · Tossou et al., 2026
Molecular Therapy · Tossou et al., 2026
After several years of collaborative research, we are pleased to share that our team's latest study has been published in Molecular Therapy.
This publication marks an important milestone in our long-term research program dedicated to developing combinatorial RNA-based therapeutic strategies inspired by extracellular vesicles (EVs).
Triple-negative breast cancer (TNBC) and pancreatic cancer remain among the most aggressive human malignancies, highlighting the need for innovative therapeutic approaches.
Our research has been driven by a simple but fundamental question:
Can the anti-tumoral activity of extracellular vesicles be recapitulated by a defined combination of regulatory microRNAs?
In this study, we demonstrate that a defined signature of 15 microRNAs recapitulates the anti-tumoral activity of NFAT3-regulated extracellular vesicles. By coordinately regulating multiple pathways involved in tumor progression, this miRNA signature reduces cancer cell proliferation and invasion while displaying significant anti-tumoral activity in preclinical models.
These findings strengthen the concept that combinatorial RNA therapeutics may offer a promising strategy to tackle the molecular complexity of aggressive cancers.
More broadly, this work represents an important step toward translating the biological activity of extracellular vesicles into defined, programmable RNA therapeutics.
This publication is both a major milestone and the beginning of a new chapter in our research toward next-generation RNA therapeutics inspired by extracellular vesicles.
Behind the paper
What if we had asked the wrong question?
Our 2026 Molecular Therapy paper did not begin with miR-Comb 15. It began several years earlier with an unexpected biological observation — and a question.
2020 — THE DISCOVERY
2020 — THE DISCOVERY
In 2020, we discovered that NFAT3-regulated extracellular vesicles (EVs) possess anti-tumoral properties, reducing cancer cell invasion and limiting tumor progression and metastasis.
Scientific reports: Camargo et al.,2026
This discovery raised a fundamental question:
What makes these EVs anti-tumoral?
A natural next step would have been to study how cancer cells respond to EV treatment: which genes are modified? Which pathways are affected?
But our goal was not only to describe the cellular response. We wanted to identify the molecular information responsible for the anti-tumoral activity of these EVs.
If we could decipher the key actors carried by these vesicles, we might ultimately be able to harness this natural mechanism and transform it into a new therapeutic strategy against cancer.
So we asked a different question:
What molecular information do these EVs actually deliver to recipient cancer cells?
FROM THE RESPONSE TO THE MESSAGE
FROM THE RESPONSE TO THE MESSAGE
Rather than focusing only on cellular responses, we investigated the RNA cargo of NFAT3-regulated EVs.
Our hypothesis was that their activity was not driven by a single molecule, but by the coordinated action of multiple regulatory RNAs.
2026 — DECODING THE MESSAGE
2026 — DECODING THE MESSAGE
This strategy provided an answer: miR-Comb 15, a combinatorial 15-miRNA signature capable of recapitulating a large part of the anti-tumoral activity of NFAT3-regulated EVs.
Our Molecular Therapy study supports a broader concept:
Complex cancers may require combinatorial RNA therapeutics capable of modulating multiple molecular networks simultaneously.
From discovering an anti-tumoral EV function to decoding its functional RNA signature, this 2020 → 2026 journey illustrates how understanding a natural biological mechanism can inspire the development of next-generation programmable RNA therapeutics.
The mechanism at a glance
How do NFAT3-regulated extracellular vesicles suppress tumor progression?
How do NFAT3-regulated extracellular vesicles suppress tumor progression?
Our study reveals how a combinatorial miRNA cargo can translate the biological activity of NFAT3-regulated extracellular vesicles into coordinated regulation of multiple tumor-associated pathways.
Take-home message
A defined 15-miRNA signature recapitulates a large part of the anti-tumoral activity of NFAT3-regulated extracellular vesicles, supporting a multi-target RNA-based strategy to address the molecular complexity of aggressive cancers.
The story continues...
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