SubsidieMeestersDeciphering non-genetic determinants and targetability of cancer cell plasticity.
This project aims to reverse cancer cell plasticity in pediatric tumors using advanced genomic techniques to develop new therapeutic strategies for effective treatment.
Projectdetails
Introduction
Cancer cell plasticity, the ability of cancer cells to change their identity, enables tumors to adapt to hostile environments, aiding metastasis and resistance to treatments. Hence, plasticity is a major unsolved problem frustrating effective treatment. Unraveling the mechanisms underlying cancer cell plasticity is crucial to establish new avenues for cancer therapy.
In contrast to adult cancers, many pediatric tumors are driven by a single genetic alteration that fuels their aggressive nature through remarkable plasticity. Despite their differences, pediatric cancers offer a unique platform to investigate cancer cell plasticity due to their genetically clear characteristics. I hypothesize that plasticity can be reversed to differentiate tumor cells and “mature cancer”.
Goal
Building upon previous ERC-StG funding, we have successfully utilized organoid technology, single-cell genomics, and lineage tracing approaches to uncover the origins of various pediatric cancers. Our findings revealed that these cancers exhibit robust yet pharmacologically reversible plasticity at the level of the epigenome.
The goal of this proposal is to reverse cell state changes during tumorigenesis to “mature cancer”.
Approach
We will:
- Apply advanced (spatial) single-cell transcriptomics and epigenomics approaches to a unique cohort of pediatric tumors and metastases to map out cell state changes during disease progression.
- Utilize our unique pediatric cancer organoids to interrogate and target hierarchical trajectories with the aim to mature cancer.
- Screen the enhancer-ome to identify non-genetic determinants of cancer cell plasticity.
Innovation
Integrating these cutting-edge technologies on patient-derived tissues and organoids will uncover fundamental principles governing cancer cell plasticity. The research will pioneer innovative methodologies and reveal strategies for identifying cancer maturation targets, advancing cancer therapy research.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 2.000.000 |
| Totale projectbegroting | € 2.000.000 |
Tijdlijn
| Startdatum | 1-6-2025 |
| Einddatum | 31-5-2030 |
| Subsidiejaar | 2025 |
Partners & Locaties
Projectpartners
- PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BVpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
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|---|---|---|---|---|
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Cancer cell plasticity on targeted therapy
This project aims to develop innovative cancer therapies by analyzing tumor heterogeneity and targeting drug-tolerant persister cells to prevent resistance and improve patient outcomes.
Oncogenic competence during development – When, Where and Why?
This project aims to uncover the origins and transformation mechanisms of malignant rhabdoid tumors through advanced genomic and imaging techniques, with the goal of developing targeted treatments.
Developmentally programmed pediatric sarcomas: a versatile platform for drug discovery and molecular precision medicine
The project aims to develop innovative in vitro and in vivo models of Ewing sarcoma using human pluripotent stem cells to enhance drug discovery and precision medicine for pediatric cancers.
Dynamics of Adaptation and Resistance in Cancer: MApping and conTrolling Transcriptional and Epigenetic Recurrence
This project aims to uncover the mechanisms of drug resistance in colorectal cancer through innovative models and computational methods, ultimately improving treatment strategies and patient outcomes.
Understanding and targeting cancer persister cells
This project aims to develop tools for studying cancer persister cells using single-cell lineage tracing to enhance understanding and treatment of therapy-resistant tumors.
Vergelijkbare projecten uit andere regelingen
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|---|---|---|---|---|
A multiplexed biomimetic imaging platform for assessing single cell plasticity (Plastomics) and scoring of tumour malignancyThe PLAST_CELL project aims to develop a microfluidics-based imaging platform to quantify cancer cell plasticity, enhancing diagnosis and treatment of metastasis and therapy resistance. | EIC Pathfinder | € 2.982.792 | 2022 | Details |
Functional chemical reprogramming of cancer cells to induce antitumor immunityThe RESYNC consortium aims to revolutionize cancer immunotherapy by reprogramming cancer cells into antigen-presenting dendritic cells using small molecules for personalized and safer treatments. | EIC Pathfinder | € 2.966.695 | 2024 | Details |
A multiplexed biomimetic imaging platform for assessing single cell plasticity (Plastomics) and scoring of tumour malignancy
The PLAST_CELL project aims to develop a microfluidics-based imaging platform to quantify cancer cell plasticity, enhancing diagnosis and treatment of metastasis and therapy resistance.
Functional chemical reprogramming of cancer cells to induce antitumor immunity
The RESYNC consortium aims to revolutionize cancer immunotherapy by reprogramming cancer cells into antigen-presenting dendritic cells using small molecules for personalized and safer treatments.