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Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine
A. Mazurakova, L. Koklesova, SH. Csizmár, M. Samec, A. Brockmueller, M. Šudomová, K. Biringer, E. Kudela, M. Pec, SM. Samuel, M. Kassayova, STS. Hassan, K. Smejkal, M. Shakibaei, D. Büsselberg, L. Saso, P. Kubatka, O. Golubnitschaja
Jazyk angličtina Země Egypt
Typ dokumentu časopisecké články, přehledy
NLK
Directory of Open Access Journals
od 2010
PubMed Central
od 2013
Europe PubMed Central
od 2020
Open Access Digital Library
od 2010-01-01
Open Access Digital Library
od 2010-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2009
- MeSH
- flavonoidy MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- glukosa metabolismus MeSH
- individualizovaná medicína MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory * farmakoterapie metabolismus MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- signální transdukce MeSH
- transkripční faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically to maintain their supply of energy and precursor molecules for biosynthesis and thus sustain rapid proliferation and tumor growth. Among the various metabolic adaptations observed in cancer cells, the altered glucose metabolism is the most widely studied. The aberrant glycolytic modification in cancer cells has been associated with rapid cell division, tumor growth, cancer progression, and drug resistance. The higher rates of glycolysis in cancer cells, as a hallmark of cancer progression, is modulated by the transcription factor hypoxia inducible factor 1 alpha (HIF-1α), a downstream target of the PI3K/Akt signaling, the most deregulated pathway in cancer. AIM OF REVIEW: We provide a detailed overview of current, primarily experimental, evidence on the potential effectiveness of flavonoids to combat aberrant glycolysis-induced resistance of cancer cells to conventional and targeted therapies. The manuscript focuses primarily on flavonoids reducing cancer resistance via affecting PI3K/Akt, HIF-1α (as the transcription factor critical for glucose metabolism of cancer cells that is regulated by PI3K/Akt pathway), and key glycolytic mediators downstream of PI3K/Akt/HIF-1α signaling (glucose transporters and key glycolytic enzymes). KEY SCIENTIFIC CONCEPTS OF REVIEW: The working hypothesis of the manuscript proposes HIF-1α - the transcription factor critical for glucose metabolism of cancer cells regulated by PI3K/Akt pathway as an attractive target for application of flavonoids to mitigate cancer resistance. Phytochemicals represent a source of promising substances for cancer management applicable to primary, secondary, and tertiary care. However, accurate patient stratification and individualized patient profiling represent crucial steps in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM / 3PM). The article is focused on targeting molecular patterns by natural substances and provides evidence-based recommendations for the 3PM relevant implementation.
Department of Natural Drugs Faculty of Pharmacy Masaryk University 61242 Brno Czech Republic
Museum of Literature in Moravia Klášter 1 66461 Rajhrad Czech Republic
Citace poskytuje Crossref.org
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