Aspirin and the metabolic hallmark of cancer: novel therapeutic opportunities for colorectal cancer.
Aspirin
adjuvant for therapy
anti-tumour
cancer metabolism
cancer prevention
colorectal cancer
metabolic hallmark
nonsteroidal anti-inflammatory drugs
Journal
Exploration of targeted anti-tumor therapy
ISSN: 2692-3114
Titre abrégé: Explor Target Antitumor Ther
Pays: United States
ID NLM: 101770662
Informations de publication
Date de publication:
2023
2023
Historique:
received:
19
01
2023
accepted:
08
06
2023
medline:
18
9
2023
pubmed:
18
9
2023
entrez:
18
9
2023
Statut:
ppublish
Résumé
Aspirin is a well-known nonsteroidal anti-inflammatory drug (NSAID) that has a recognized role in cancer prevention as well as evidence to support its use as an adjuvant for cancer treatment. Importantly there has been an increasing number of studies contributing to the mechanistic understanding of aspirins' anti-tumour effects and these studies continue to inform the potential clinical use of aspirin for both the prevention and treatment of cancer. This review focuses on the emerging role of aspirin as a regulator of metabolic reprogramming, an essential "hallmark of cancer" required to support the increased demand for biosynthetic intermediates needed for sustained proliferation. Cancer cells frequently undergo metabolic rewiring driven by oncogenic pathways such as hypoxia-inducible factor (HIF), wingless-related integration site (Wnt), mammalian target of rapamycin (mTOR), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB), which supports the increased proliferative rate as tumours develop and progress. Reviewed here, cellular metabolic reprogramming has been identified as a key mechanism of action of aspirin and include the regulation of key metabolic drivers, the regulation of enzymes involved in glycolysis and glutaminolysis, and altered nutrient utilisation upon aspirin exposure. Importantly, as aspirin treatment exposes metabolic vulnerabilities in tumour cells, there is an opportunity for the use of aspirin in combination with specific metabolic inhibitors in particular, glutaminase (GLS) inhibitors currently in clinical trials such as telaglenastat (CB-839) and IACS-6274 for the treatment of colorectal and potentially other cancers. The increasing evidence that aspirin impacts metabolism in cancer cells suggests that aspirin could provide a simple, relatively safe, and cost-effective way to target this important hallmark of cancer. Excitingly, this review highlights a potential new role for aspirin in improving the efficacy of a new generation of metabolic inhibitors currently undergoing clinical investigation.
Identifiants
pubmed: 37720350
doi: 10.37349/etat.2023.00155
pmc: PMC10501897
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
600-615Informations de copyright
© The Author(s) 2023.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest.
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