Quercetin in Cancer Therapy: Molecular Mechanisms, Delivery Strategies, Clinical Prospects, and Safety

Quercetin, a naturally occurring flavonol found abundantly in fruits, vegetables, and medicinal plants, has gained considerable attention for its diverse pharmacological properties and therapeutic potential in cancer treatment. Preclinical evidence highlights its multifaceted biological activities, including antioxidant, anti-inflammatory, pro-apoptotic, and anti-angiogenic effects, which collectively target several hallmarks of cancer. Quercetin exerts its anticancer effects by modulating key molecular pathways such as PI3K/Akt, MAPK, NF-κB, and Nrf2, thereby influencing cell proliferation, apoptosis, metastasis, and regulation of the tumor microenvironment. Despite promising laboratory and animal model data, its poor solubility, low bioavailability, and rapid metabolism limit its clinical application. Drug delivery systems such as nanoparticle formulations, liposomes, and micelles have shown potential to overcome these barriers and enhance therapeutic efficacy. Moreover, combination therapies of quercetin with conventional chemotherapeutics demonstrate synergistic effects, offering improved efficacy and reduced toxicity. While early clinical trials and supportive-care applications suggest a favorable safety profile, concerns regarding pharmacokinetics, drug-nutrient interactions, and dose-related side effects remain unresolved. This review summarizes the current knowledge of quercetin's molecular mechanisms, delivery strategies, safety considerations, and clinical prospects, and provides perspectives for future research aimed at optimizing its role as an adjuvant or standalone anticancer agent.