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Identification of long non-coding RNA-based biomarkers of immunotherapy response in Triple-Negative Breast Cancer via liquid biopsy profiling

Objective

Triple-negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer, characterized by the absence of estrogen receptor, progesterone receptor and HER2 expression. This lack of molecular targets limits treatment options and highlights the urgent need of novel therapeutic strategies. While immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have shown promise in early-stage TNBC, response rates remain variable and difficult to predict. Recent studies have implicated long non-coding RNAs (lncRNAs) as key regulators of immune-related pathways, suggesting their potential as modulators of immunotherapy sensitivity.

The Triple-R project aims to identify and functionally characterize lncRNA-based biomarkers predictive of response to neoadjuvant immunotherapy in early TNBC. The specific objectives to achieved this are: 1) To compare lncRNA expression profiles, integrating RNA-sequencing data from tumour tissue and liquid biopsy samples —including exosomes, circulating tumour cells and cell-free RNA— collected from patients undergoing treatment. 2) To infer lncRNA expression from cell-free DNA fragmentomics. 3) To characterize the functional role of selected lncRNAs through CRISPR-based knockdown or overexpression in selected TNBC cell lines under ICIs treatment, assessing the impact on cell proliferation and relative fitness. Furthermore, the project will benefit from an international collaboration (Peter MacCallum Cancer Centre, Australia), with complementary results from the BCT 1702-CHARIOT clinical trial that will enhance the robustness and translational relevance of the findings.

The proposal introduces innovative approaches to advance precision oncology, focusing on gene expression profiling via liquid biopsy. By identifying novel potential biomarkers and lncRNA signatures linked to immunotherapy sensitivity, it aims to improve patient stratification and enable more effective, personalized treatment strategies for TNBC.

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Keywords

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Topic(s)

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

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Call for proposal

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

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Coordinator

FUNDACION PARA LA INVESTIGACION DE MALAGA EN BIOMEDICINA Y SALUD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 194 074,56
Address
CALLE SEVERO OCHOA 35, PARQUE TECNOLOGICO DE ANDALUCIA
29590 MALAGA
Spain

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Region
Sur Andalucía Málaga
Activity type
Research Organisations
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Total cost

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