Flavonoids in cancer pharmacology: molecular mechanisms, tumor microenvironment regulation, and drug resistance
- 1Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
- 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- 3The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
Abstract
Flavonoids are structurally diverse polyphenolic compounds that influence multiple processes involved in cancer development and treatment response. This review summarizes the reported effects of structurally defined flavonoids on tumor cell proliferation, regulated cell death, oncogenic and epigenetic signaling, metabolic adaptation, the tumor microenvironment, angiogenesis, and therapy resistance. PubMed, Web of Science, and Scopus were searched for literature published primarily from 2016 to July 2026 using terms related to flavonoids, representative flavonoid compounds, cancer-associated mechanisms, drug resistance, combination therapy, drug delivery, pharmacokinetics, bioavailability, and safety. Earlier landmark and mechanistic studies were included when necessary to provide historical context or support established pathways. Experimental evidence indicates that flavonoids can modulate cell cycle progression, apoptosis and other regulated cell death pathways, inflammatory and immune signaling, tumor metabolism, drug efflux transporters, epithelial to mesenchymal transition, and epigenetic programs associated with resistance. Their effects are nevertheless dependent on compound structure, dose, tumor model, cellular redox state, and treatment context. Combination and nanodelivery strategies may improve experimental activity or exposure, but their interpretation requires consideration of quantitative drug interactions, active metabolites, pharmacokinetic changes, and safety. Most available evidence remains preclinical, and clinical translation is constrained by limited bioavailability, extensive metabolism, heterogeneous tumor responses, and possible interactions with anticancer drugs. Further development should therefore emphasize chemically defined compounds, clinically achievable exposure, functional validation of proposed mechanisms, standardized formulations, and integrated pharmacokinetic and safety assessment.
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BibTeX
@article{yu2026flavonoids,
title = {{Flavonoids in cancer pharmacology: molecular mechanisms, tumor microenvironment regulation, and drug resistance}},
author = {Zhengyuan Yu and Zhanyi Zhou and Ni Yin and Hongcheng Ge},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1969337},
url = {https://doi.org/10.3389/fphar.2026.1969337},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Flavonoids in cancer pharmacology: molecular mechanisms, tumor microenvironment regulation, and drug resistance
AU - Zhengyuan Yu
AU - Zhanyi Zhou
AU - Ni Yin
AU - Hongcheng Ge
PY - 2026
DA - 2026/10/12
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1969337
UR - https://doi.org/10.3389/fphar.2026.1969337
AB - Flavonoids are structurally diverse polyphenolic compounds that influence multiple processes involved in cancer development and treatment response. This review summarizes the reported effects of structurally defined flavonoids on tumor cell proliferation, regulated cell death, oncogenic and epigenetic signaling, metabolic adaptation, the tumor microenvironment, angiogenesis, and therapy resistance. PubMed, Web of Science, and Scopus were searched for literature published primarily from 2016 to July 2026 using terms related to flavonoids, representative flavonoid compounds, cancer-associated mechanisms, drug resistance, combination therapy, drug delivery, pharmacokinetics, bioavailability, and safety. Earlier landmark and mechanistic studies were included when necessary to provide historical context or support established pathways. Experimental evidence indicates that flavonoids can modulate cell cycle progression, apoptosis and other regulated cell death pathways, inflammatory and immune signaling, tumor metabolism, drug efflux transporters, epithelial to mesenchymal transition, and epigenetic programs associated with resistance. Their effects are nevertheless dependent on compound structure, dose, tumor model, cellular redox state, and treatment context. Combination and nanodelivery strategies may improve experimental activity or exposure, but their interpretation requires consideration of quantitative drug interactions, active metabolites, pharmacokinetic changes, and safety. Most available evidence remains preclinical, and clinical translation is constrained by limited bioavailability, extensive metabolism, heterogeneous tumor responses, and possible interactions with anticancer drugs. Further development should therefore emphasize chemically defined compounds, clinically achievable exposure, functional validation of proposed mechanisms, standardized formulations, and integrated pharmacokinetic and safety assessment.
SN - 1663-9812
ER -