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Reversing metabolic reprogramming in obesity-associated hepatocellular carcinoma by inhibiting receptor protein tyrosine phosphatases

Objective

REPRO-PTP is addressing the critical need for effective treatments in obesity-associated hepatocellular carcinoma (HCC). HCC, which accounts for 90% of primary liver cancers, is refractory to conventional chemotherapy with very low survival rate. As obesity is a major risk factor for HCC, it is imperative to develop new therapeutic approaches. My laboratory has identified receptor protein tyrosine phosphatases (PTPs) as key regulators of glycolysis and lipogenesis, with PTPRK emerging as a particularly promising target. Mechanistically, PTPRK is selectively increased in tumorigenic hepatocytes, inactivating fructose-1,6-bisphosphatase 1 (FBP1) and promoting glycolysis. PTPRK-mediated glycolysis increases peroxisome proliferator-activated receptor (PPAR)γ-dependent lipogenic signalling and HCC progression in obesity. REPRO-PTP aims to optimize and validate new PTPRK inhibitors that exhibit high selectivity, potency, and in vivo activity. By targeting both hepatic glycolysis and lipogenesis, these inhibitors have the unique potential to improve treatment outcomes for HCC in obese patients by reducing cancer progression and relapse risk. We will provide a robust pipeline for the broader development of PTPRK and additional PTP inhibitors for translational applicability, devise an intellectual property strategy, and perform a commercial feasibility analysis. The project represents a collaborative effort involving experts in oncology, biochemistry, and pharmacology, and is expected to yield novel insights into PTPs as drug targets in cancer and metabolic diseases. REPRO-PTP aims to pave the way for the development of innovative therapies that can improve the quality of life and survival rates for patients suffering from HCC and potentially other obesity-related hepatic complications.

Fields of science (EuroSciVoc)

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Programme(s)

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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-POC - HORIZON ERC Proof of Concept 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-2024-POC

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Host institution

UNIVERSITE LIBRE DE BRUXELLES
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.

€ 150 000,00
Address
AVENUE FRANKLIN ROOSEVELT 50
1050 Bruxelles / Brussel
Belgium

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Higher or Secondary Education Establishments
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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.

No data

Beneficiaries (1)

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