Project description
Epigenetic modifications in cancer drug resistance
Drug resistance in cancer represents a significant challenge in treatment and results from genetic mutations, the tumour microenvironment, and epigenetic changes. Understanding these mechanisms is crucial for developing effective strategies to overcome resistance and improve cancer treatment outcomes. Funded by the European Research Council, the EpiResist project focuses on the role of RNA modifications in cancer drug resistance. The aim is to develop a method for mapping N6-methyladenosine (m6A) modifications at the single cell level and to apply it to triple-negative breast cancer cells to identify resistance targets. Through a unique analysis, the project envisions to unveil new epigenetic characteristics and potential therapeutic interventions within the rising research field of epitranscriptomics.
Objective
Drug resistance is one of the biggest challenges in the clinical management of breast cancer (BC), but the underlying mechanisms are still not fully understood. What we do know is that epigenetic mechanisms play a key role in the adaptation of cancer cells to therapy, which is why they have become a prime field of investigation. Single-cell profiling of epigenetic DNA and histone modifications have already revealed intriguing and actionable insights into tumor heterogeneity. For the most recently discovered epigenetic layer however, which consists of RNA modifications, we have not yet reached single-cell resolution. The exciting potential of RNA modifications to fine-tune the processing and expression of mRNAs is currently an area of intense research termed ‘Epitranscriptomics’ and the most prevalent and best studied of these mRNA modifications, N6-methyladenosine (m6A), has recently been linked to drug resistance in cancer. Our lab has uncovered a new m6A-based layer of dysregulation of a major cancer pathway driving therapy resistance in BC. The ability to study m6A in single cells holds great promise as it would enable us to further delineate tumor heterogeneity and to find novel drug resistance targets that have eluded us so far. I propose to develop a method for streamlined m6A mapping at single-cell resolution (Aim 1), to apply it to triple-negative BC (TNBC) cells driven to chemoresistance in cell culture, mice, and human samples so as to determine uncharted targets of drug resistance (Aim 2), and to disrupt m6A-regulated chemoresistance targets in order to prevent therapy failure (Aim 3). These aims are aligned with my knowledge and skills related to both m6A and drug resistance. This unique and comprehensive analysis of the single-cell m6A methylome will provide invaluable new insights into the unknown epigenetic characteristics of chemoresistance and will pave the way for new therapeutic interventions.
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 DNA
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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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.1.1 - European Research Council (ERC)
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Topic(s)
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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-ERC - HORIZON ERC Grants
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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) ERC-2023-STG
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1050 Bruxelles / Brussel
Belgium
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