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Targeting EP300/CBP in AML: from mechanistic discovery to therapeutic innovation

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.

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Keywords

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Programme(s)

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Topic(s)

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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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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) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITA DEGLI STUDI DI PARMA
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.

€ 193 643,28
Address
VIA UNIVERSITA 12
43121 PARMA
Italy

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Region
Nord-Est Emilia-Romagna Parma
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