An insight into thymidylate synthase inhibitor as anticancer agents: an explicative review.

Cancer Chemotherapy Folate Thymidylate synthase Thymidylate synthase inhibitor miRNA

Journal

Naunyn-Schmiedeberg's archives of pharmacology

ISSN: 1432-1912

Titre abrégé: Naunyn Schmiedebergs Arch Pharmacol

Pays: Germany

ID NLM: 0326264

Informations de publication

Date de publication:
06 Mar 2024

Historique:

received: 05 02 2024

accepted: 20 02 2024

medline: 6 3 2024

pubmed: 6 3 2024

entrez: 6 3 2024

Statut: aheadofprint

Résumé

Cancer, a widespread challenge to global health, remains a puzzle of intricate molecular dynamics. This review article delves into the mystery of cancer, with a keen focus on understanding the contributory role of thymidylate synthase (TS) in cancer. TS, a vital enzyme in DNA synthesis and repair, emerges as a significant player in the narrative of cancer development. The conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) is a major step in producing DNA. Numerous malignancies, including those of the breast, colon, lung, and ovary, have been linked to dysregulation of TS activity. Overexpression or mutations of TS lead to uncontrolled cell proliferation and tumorigenesis molecular interactions and signalling pathways involving TS come under scrutiny, revealing the nuanced connections that propel its involvement in cancer progression. Beyond overexpression and mutations, there emerges a subtle layer of regulation that involves microRNAs (miRNAs). These tiny particles attach to the TS messenger RNA, causing translational repression or its degradation, which in turn affects TS activity. Moving towards the therapeutic realm, thymidylate synthase inhibition acts as a promising anti-cancer strategy. Targeting TS with small-molecule inhibitors could provide a novel approach to treat various cancers. By reducing the number of available nucleotides, TS inhibition would slow down or halt cancer cell division, thus depriving the tumor of the building blocks required for its proliferation and growth. The aim is to assess the viability and effectiveness of targeting TS to halt or slow down cancer progression. There is growing evidence that, in comparison to traditional TS inhibitors, few novel antifolate TS inhibitors are effective against a wider variety of neoplasms, such as lung carcinomas. It has been discovered that TS inhibitors increase cancer tissues' sensitivity to chemotherapy and radiation, increasing their vulnerability to these treatments. This article aims to provide a comprehensive insight into TS, examining its cellular details, detailing the heterocyclic moieties and molecular foundations, and providing a promising future outlook.

Identifiants

DOI: 10.1007/s00210-024-03020-y PMID: 38446215

pubmed: 38446215

doi: 10.1007/s00210-024-03020-y

pii: 10.1007/s00210-024-03020-y

doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

Informations de copyright

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