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Deciphering the dynamic-plasticity and heterogeneity of cancer-associated fibroblasts

Objective

Cancer-associated fibroblasts (CAFs) are one of the most abundant and versatile cell types in the tumour microenvironment (TME), where they crosstalk with stromal cells and actively participate in tumour development. Because of their assumed pro-tumourigenic functions, CAFs have long been considered an attractive therapeutic target. However, recent evidence indicates that multiple CAF subpopulations showing inflammatory, myofibroblastic, vascular, antigen-presenting, and immunosuppressive phenotypes co-exist within the same tumour, with some promoting and other restricting tumour growth; thus, making their targeting challenging. How CAFs change dynamically as cancers evolve, and how this may affect the overall tumour heterogeneity, remains unaddressed. Therefore, the main goal of DynamHet is to elucidate the origin and evolution of CAF heterogeneity and to decipher the mediators and mechanisms that regulate CAF plasticity as the tumour advances. This is crucial for the development of effective therapies aimed at reprogramming CAFs towards therapeutically favourable phenotypes and will constitute a great breakthrough in the field of oncology. Hence, DynamHet aims to 1) decipher the origin of CAF heterogeneity by performing clonal tracing and by generating and characterising CAF subtypes starting from human induced pluripotent stem cells; 2) dissect CAF-TME crosstalk by generating 3D patient-derived organoids and spheroids and by analysing their secretome and transcriptomic profiles using high throughput technologies and computational analysis; and 3) reprogramme CAFs by genetic manipulation in favour of therapeutically advantageous subpopulations as a novel therapeutic approach. DynamHet is an ambitious and feasible project that stands as a pioneer in the new concept of deciphering the origin and reprogramming the dynamic heterogeneity of CAFs towards the development of innovative precision medicine approaches in cancer.

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Keywords

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Programme(s)

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Topic(s)

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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-2022-STG

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Host institution

FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
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.

€ 1 775 190,00
Address
CARRER ROSSELLO 149
08036 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
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.

€ 1 775 190,00

Beneficiaries (1)

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