Project description
Metabolic targeting of liver cancer
Individuals with type 2 diabetes face a much higher risk of liver cancer due to chronic inflammation and altered metabolism. However, the biological links between diabetes and liver cancer remain poorly understood. With the support of the Marie Skłodowska-Curie Actions programme, the IRM project will investigate the enzymes GLS and GLS2 that help cells use glutamine, an important nutrient for energy and survival. Using advanced mouse models, metabolic testing, imaging, and single-cell analysis, researchers will study how these enzymes drive tumour growth flexibility and immune escape. The project will also examine sex differences and develop smarter combination treatments for patients with diabetes-associated liver cancer, improving future care outcomes.
Objective
Hepatocellular carcinoma (HCC), the most common primary liver cancer, has survival rates below 20%. Type 2 diabetes (T2D) markedly increases HCC incidence by driving metabolic and inflammatory changes, but the underlying mechanisms are unclear. Emerging evidence points to altered glutamine metabolism via the glutaminase isoenzymes GLS and GLS2 as a key link, though its role in diabetes-driven HCC remains unexplored.
This project aims to elucidate how GLS and GLS2 regulate tumor bioenergetics, metabolic flexibility, and immune evasion in T2D-associated HCC, and to assess whether targeting these isoenzymes offers a viable therapeutic approach. The specific aims are:
1) Characterize the roles of GLS and GLS2 in tumorigenesis and metabolic reprogramming in diabetes-associated HCC using CD-HFD mouse models.
2) Dissect the distinct roles of GLS and GLS2 in regulating tumor bioenergetics and metabolic reprogramming in HCC to be used as targets in liver cancer.
3) Design a therapeutic strategy for diabetes-driven HCC including GLS and GLS2 through their impact in the tumor microenvironment, focusing on immune cell infiltration, activation status of both isoenzymes, and their immunosuppressive mechanisms.
To achieve these goals, the study will employ physiologically relevant mouse models of metabolic syndrome–driven HCC, complemented by advanced methodologies including Seahorse metabolic flux assays, live-cell imaging, metabolomics, and single-cell RNA sequencing to dissect tumor–stromal–immune interactions. Sex-specific differences will also be systematically investigated.
The project will generate new mechanistic insights into the metabolic crosstalk between diabetes and liver cancer, uncovering therapeutic vulnerabilities that target glutamine dependence while overcoming tumor heterogeneity and resistance. Expected outcomes include the rational design of combinatorial therapies tailored to metabolic disease–associated HCC.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
- medical and health sciences clinical medicine oncology liver cancer
- natural sciences biological sciences cell biology cell metabolism
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics RNA transcriptomes
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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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.
29590 MALAGA
Spain
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.