Descrizione del progetto
Modificazioni epigenetiche nella resistenza ai farmaci antitumorali
La resistenza ai farmaci antitumorali, una sfida significativa nel trattamento del cancro, deriva da mutazioni genetiche, dal microambiente tumorale e da cambiamenti epigenetici. La comprensione di questi meccanismi è fondamentale per sviluppare strategie efficaci volte a superare la resistenza e migliorare gli esiti dei trattamenti oncologici. Finanziato dal Consiglio europeo della ricerca, il progetto EpiResist si concentra sul ruolo svolto dalle modifiche dell’RNA nella resistenza ai farmaci antitumorali con l’obiettivo di sviluppare un metodo per mappare le modifiche della N6-metiladenosina (m6A) a livello di singola cellula e di applicarlo alle cellule cancerose del tumore al seno triplo negativo al fine di identificare i bersagli della resistenza. Attraverso lo svolgimento di un’analisi unica, il progetto prevede di svelare nuove caratteristiche epigenetiche e potenziali interventi terapeutici nel campo di ricerca in ascesa dell’epitrascrittomica.
Obiettivo
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.
Campo scientifico
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
1050 Bruxelles / Brussel
Belgio