A novel view on an old drug, 5-fluorouracil: an unexpected RNA modifier with intriguing impact on cancer cell fate.
Journal
NAR cancer
ISSN: 2632-8674
Titre abrégé: NAR Cancer
Pays: England
ID NLM: 101769553
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
18
03
2021
revised:
01
07
2021
accepted:
09
08
2021
entrez:
19
8
2021
pubmed:
20
8
2021
medline:
20
8
2021
Statut:
epublish
Résumé
5-Fluorouracil (5-FU) is a chemotherapeutic drug widely used to treat patients with solid tumours, such as colorectal and pancreatic cancers. Colorectal cancer (CRC) is the second leading cause of cancer-related death and half of patients experience tumour recurrence. Used for over 60 years, 5-FU was long thought to exert its cytotoxic effects by altering DNA metabolism. However, 5-FU mode of action is more complex than previously anticipated since 5-FU is an extrinsic source of RNA modifications through its ability to be incorporated into most classes of RNA. In particular, a recent report highlighted that, by its integration into the most abundant RNA, namely ribosomal RNA (rRNA), 5-FU creates fluorinated active ribosomes and induces translational reprogramming. Here, we review the historical knowledge of 5-FU mode of action and discuss progress in the field of 5-FU-induced RNA modifications. The case of rRNA, the essential component of ribosome and translational activity, and the plasticity of which was recently associated with cancer, is highlighted. We propose that translational reprogramming, induced by 5-FU integration in ribosomes, contributes to 5-FU-driven cell plasticity and ultimately to relapse.
Identifiants
pubmed: 34409299
doi: 10.1093/narcan/zcab032
pii: zcab032
pmc: PMC8364333
doi:
Types de publication
Journal Article
Langues
eng
Pagination
zcab032Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Cancer.
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