Project description
Targeting epigenetic dependencies in acute myeloid leukaemia
Acute myeloid leukaemia (AML) remains difficult to treat because current therapies are often not curative. Epigenetic therapies have emerged as a promising strategy for AML. Supported by the Marie Skłodowska-Curie Actions programme, the EPIC-AML project is investigating the efficacy of targeting the bromodomain of the epigenetic regulators EP300/CBP in AML. It will identify drug combinations that act synergistically with EP300/CBP bromodomain inhibitors to strengthen anti-leukaemic effects. It will also map the functional regions of EP300/CBP that are essential for cancer cell survival and uncover key protein interactors that could serve as new drug targets. The work will combine drug screening and functional genomics alongside training and dissemination activities. Overall, the project aims to open new therapeutic strategies for AML patients.
Objective
EP300 and CBP are crucial lysine acetyltransferases regulating enhancer-dependent transcription via scaffolding and enzymatic activities. They are appealing targets in cancer due to their role in cell cycle control and their druggability. In particular, small molecules targeting the EP300/CBP bromodomains have shown promising activity in haematological malignancies. CCS1477, the first clinical-grade EP300/CBP bromodomain inhibitor, has demonstrated encouraging preclinical and early-phase clinical activity in Acute Myeloid Leukaemia (AML) and Multiple Myeloma (MM). It induces cell cycle arrest and differentiation by displacing EP300/CBP from enhancer sites occupied by key transcription factors (TFs). However, only a subset of patients responds effectively to CCS1477 monotherapy. This project aims to identify novel synergistic drug combinations involving EP300/CBP bromodomain inhibitors to enhance their therapeutic efficacy in AML. Beyond the bromodomain, it will define the regions of EP300/CBP essential for AML growth and uncover functional, potentially targetable interactors bound at these sites to guide future drug development. During the MSCA fellowship, the researcher will spend 24 months at the University of Parma (UNIPR), under the supervision of Prof. Giovanni Roti, an expert in functional genomics and high-throughput drug screening in blood cancers. These approaches are critical for project success and represent key transferable skills for the researcher’s career. The fellow will undertake professional development and scientific training courses, attend seminars and international conferences, prepare two manuscripts for submission to high-impact journals, and organise public engagement activities to maximise the project’s impact within both the scientific and lay communities. This fellowship will significantly advance Dr. Nicosia’s career and support his long-term goal of leading an independent research group in translational epigenetics in blood cancer.
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.
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.
- natural sciences biological sciences genetics
- medical and health sciences clinical medicine oncology
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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.
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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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(opens in new window) HORIZON-MSCA-2025-PF
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43121 PARMA
Italy
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.