Towards a druggable epitranscriptome : Compounds that target RNA modifications in cancer
Berdasco, Maria (Institut d'Investigació Biomèdica de Bellvitge)
Esteller, M (Institució Catalana de Recerca i Estudis Avançats)

Data:	2022
Resum:	Epitranscriptomics is an exciting emerging area that studies biochemical modifications of RNA. The field has been opened up by the technical efforts of the last decade to characterize and quantify RNA modifications, and this has led to a map of post-transcriptional RNA marks in normal cell fate and development. However, the scientific interest has been fuelled by the discovery of aberrant epitranscriptomes associated with human diseases, mainly cancer. The challenge is now to see whether epitrancriptomics offers mechanisms that can be effectively targeted by low MW compounds and are thus druggable. In this review, we will describe the principal RNA modifications (with a focus on mRNA), summarize the latest scientific evidence of their dysregulation in cancer and provide an overview of the state-of-the-art drug discovery to target the epitranscriptome. Finally, we will discuss the principal challenges in the field of chemical biology and drug development to increase the potential of targeted-RNA for clinical benefit. LINKED ARTICLES: This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary. wiley. com/doi/10. 1111/bph. v179. 12/issuetoc.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1080 Ministerio de Economía y Competitividad PI15/00638 Instituto de Salud Carlos III PI18/00910 Agencia Estatal de Investigación RTI2018-094049-B-I00 "la Caixa" Foundation GN18/51140001
Nota:	We thank CERCA Programme/Generalitat de Catalunya for institutional support. Research at M.B. lab is supported by Instituto de Salud Carlos III co-funded by European Regional Development Funds (ERDF/FEDER) a way to build Europe (PI15/00638 and PI18/00910). Research at M.E. lab is supported by the Health Department PERIS-project no. SLT/002/16/00374 and AGAUR-projects no. 2017SGR1080 of the Catalan Government (Generalitat de Catalunya); Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI) and European Regional Development Fund (ERDF) project no. RTI2018-094049-B-I00 and the Cellex Foundation; 'la Caixa' Banking Foundation (LCF/PR/GN18/51140001). M.E. is an ICREA Research Professor.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article de revisió ; recerca ; Versió publicada
Matèria:	A-to-I-editingcancer ; Epitranscriptomics ; Pseudouridine ; RNA methylation ; Small-moleculeinhibitors ; Therapy
Publicat a:	British Journal of Pharmacology, Vol. 179 Núm. 12 (june 2022) , p. 2868-2889, ISSN 1476-5381

DOI: 10.1111/bph.15604

22 p, 4.4 MB

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