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Deconvolution of tumor evolution and ecosystem through EV-based liquid biopsy

Project description

Liquid biopsy that captures cancer complexity

The tumour microenvironment plays a central role in cancer development, progression and treatment resistance. Tracking how both tumours and their surrounding ecosystem co-evolve during treatment is essential for personalising cancer therapy. However, liquid biopsies capture only tumour-specific changes. To address this limitation, the ERC-funded EVOLVE project builds on an innovative RNA-profiling platform capable of distinguishing tumour-specific molecular signals from broader changes arising in the microenvironment. By analysing RNA carried in tiny membrane-bound vesicles shed into the bloodstream, researchers will decode how tumours and their surrounding immune and stromal ecosystems adapt to treatment. These insights will enable more accurate disease monitoring and guide the development of personalised therapeutic strategies for cancer patients.

Objective

Cancer progression and drug resistance are driven not only by tumor-intrinsic factors but also by complex interactions between tumor cells and their evolving microenvironment. Understanding the longitudinal co-evolution of tumors and their microenvironment is critical for developing personalized therapeutic strategies, including optimizing immunotherapeutic approaches.
Liquid biopsies provide a minimally invasive approach for longitudinal monitoring of cancer dynamics. Current methods primarily focus on next-generation sequencing-based analysis of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs), which track only tumor-specific changes during disease progression. However, other sources, such as extracellular vesicle RNA (EV-RNA) profiling, can capture broader transcriptomic changes in response to therapy. This capability is exemplified by our RExCuE (mRNA Expression in Circulating EVs) platform, an innovative tool that monitors mRNA alterations in circulation. However, RExCuE is currently unable to distinguish tumor-specific changes from systemic effects. To address this gap, I will build upon my expertise in EV-RNA analysis to understand tumor-intrinsic pathways and the activation status of tumor-extrinsic factors, including the tumor stroma and immune ecosystem. In particularly, I will: (1) identify tumor-specific EV-RNA alterations associated with therapy response and disease progression; (2) characterize the impact of ecosystem-derived EVs on tumor evolution and therapy outcomes; and (3) develop a comprehensive tool to deconvolute tumor-intrinsic and extrinsic transcriptomic changes from clinical samples in circulation.
This approach intends to provide a deeper understanding of the adaptive responses of both tumors and their ecosystems to treatments, ultimately guiding more effective and personalized therapeutic strategies.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-STG

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Host institution

FUNDACION DE LA COMUNIDAD VALENCIANA CENTRO DE INVESTIGACION PRINCIPE FELIPE
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.

€ 1 987 583,00
Address
CALLE EDUARDO PRIMO YUFERA 3
46012 VALENCIA
Spain

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Region
Este Comunitat Valenciana Valencia/València
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 987 583,00

Beneficiaries (1)

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