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Decreasing Pancreatic Adenocarcinoma-related Inflammation using small molecule inhibitors of STING

Project description

A novel approach to tackle cancer inflammation

Nucleic acid recognition by innate immune system receptors is an inherent antimicrobial strategy that activates the production of proinflammatory mediators and causes inflammation. Since chronic inflammation may cause carcinogenesis, tackling this pathway may serve as an anti-cancer strategy. The EU-funded DIM-CrIC project has discovered a novel pathway that can block nucleic acid-induced chronic inflammation by antagonising the key trigger protein STING. Scientists will develop and apply small molecules to activate this novel pathway and regulate inflammation in pancreatic ductal adenocarcinoma. The project's findings will pave the way for the control of STING-dependent inflammation as a treatment of various types of cancer.

Objective

We will develop and test a treatment for pancreatic ductal adenocarcinoma (PDAC). To this aim, we will synthesize and evaluate the efficacy of novel inhibitors of nucleic acid-induced inflammation that we have identified. Indeed, nucleic acid-induced chronic inflammation is a major driver of tumorigenesis. Because the canonical pathway that triggers nucleic acid-induced chronic inflammation relies on the STING protein, identifying ways to activate or inhibit STING is a major goal of current research.
We have identified a novel endogenous pathway that antagonizes STING though the production of a second messenger molecule. This pathway prevents spurious STING activation and regulates nucleic acid-associated inflammation. We have developed a set of analogues of this small molecules for wich we demonstrate the ability to prevent STING activation in vitro and now wish to ameliorate the intracellular delivery of these molecules to assess their in vivo efficacy on PDAC-associated inflammation. PDAC is a suitable model for establishing the proof of concept of efficacy of the treatment we propose, because we show that knocking-out STING impairs PDAC growth. Therefore, DIM-CriC will provide novel means to tackle STING-dependent inflammation in PDAC. Ultimately, this work should pave the way to assessment in additional tumorigenesis models that present a STING-dependent inflammatory profile, unraveling a novel route to block cancer-related inflammation to the benefit of patients.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-POC - Proof of Concept Grant

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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-2019-PoC

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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
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.

€ 140 200,00
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.

No data

Beneficiaries (2)

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