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Radiation-Induced Resistance in Triple-Negative Breast Cancer Organoids: Decoding the Role of Dose Fractionation and the Tumour Microenvironment in Precision Radiotherapy

Project description

Understanding radiotherapy resistance in triple-negative breast cancer

Triple-negative breast cancer is an aggressive subtype that lacks effective targeted therapies. Radiotherapy is the preferred treatment, but up to 40% of patients develop resistance. Improving radiotherapy outcomes requires better experimental models that capture the complexity of the tumour microenvironment. With the support of the Marie Skłodowska-Curie Actions programme, the RIoBORG project uses patient-derived tumour organoids to study radiotherapy resistance under clinically relevant conditions. A novel 3D co-culture system incorporating stromal and endothelial cells will model key resistance drivers, including hypoxia, inflammation, and abnormal blood vessel formation. Researchers will combine different types of molecular profiling to identify predictive biomarkers and resistance signatures. The project is expected to guide personalised radiotherapy strategies for patients with triple-negative breast cancer.

Objective

Radiotherapy fails in up to 40% of triple-negative breast cancer (TNBC) patients due to radioresistance mechanisms that remain poorly understood. RIoBORG (Radiation-Induced Resistance in Breast Cancer Organoids) addresses this urgent challenge using patient-derived xenograft organoids (PDXOs) as physiologically relevant models to study tumour-intrinsic and microenvironment-driven resistance.
This translational project advances PDXO applications by integrating clinically relevant fractionated RT protocols with advanced tumour microenvironment (TME) modelling. The study simulates clinical RT regimens under normoxic and hypoxic conditions to capture tumour heterogeneity. A novel 3D co-culture system combining PDXOs with stromal and endothelial cells will enable in-depth investigation of angiogenesis, inflammation, and hypoxia-induced radioresistance—key factors often overlooked in conventional models.
A multi-modal strategy, encompassing functional assays, molecular phenotyping, and transcriptomic analysis, will facilitate the identification of radiosensitivity-associated signatures and predictive biomarkers in PDXOs. Expected outputs include RT response profiles, biomarker panels, and stratification models that inform personalized treatment planning.
The fellowship is strengthened by the host’s expertise in organoid and molecular profiling platforms and complemented by the fellow’s background in radiobiology, immunology, and bioinformatics. This synergy ensures interdisciplinary training aligned with MSCA goals and impactful research to improve personalized RT strategies in TNBC care.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 226 420,56
Address
RUE MICHEL ANGE 3
75794 Paris
France
Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
No data