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Cancer cell plasticity on targeted therapy

Objective

Novel cancer molecular-targeted therapies allow to significantly prolong the survival of cancer patients. However, the inevitable acquisition of resistance mechanisms limits the clinical benefit of these treatments. To fully understand how resistance develops, it is crucial to better integrate tumor heterogeneity, cancer cell plasticity and microenvironment changes by applying cutting-edge single cell technologies directly on sequentially sampled biopsies from cancer patients.

Additionally, to achieve deeper and longer-lasting clinical responses for cancer patients, we will need to target the rare drug-tolerant persister cancer cells. Samples collected before, during and after treatment will be used to fully describe the characteristics of the cells that are the source of genetic resistant variants that ultimately give rise to tumor relapses. By combining the establishment of patient-derived models, drug-screening of epigenetic inhibitors, transcriptomic and epigenetic characterization of persister cells we will aim to highlight their vulnerabilities.

Finally, identify the driver mechanisms of genomic evolution by elucidating the link between oncogenic kinases and DNA repair pathways activity will be our innovative strategy to exploit putative susceptibilities to impeach the survival of resistant cells. The use of DNA repair substrate combined with CRISPR gene knockout will aim at confirming the value of targeting DNA repair pathways to profoundly transform the outcome of patients with metastatic cancer.

Overall, by applying new technological breakthrough at the single cell level on patient biopsies, digging into the intrinsic nature of persister cells and taking advantages of DNA repair defects we will identify innovative treatment strategies to avoid the emergence of resistance in patients.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2021-COG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
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.

€ 1 492 500,00
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.

€ 2 000 000,00

Beneficiaries (2)

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