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Cisplatin + quercetin is an experimental combination therapy consisting of the platinum-based chemotherapeutic agent cisplatin and the natural flavonoid quercetin. This combination has been studied primarily in preclinical models for its potential to enhance anti-tumor efficacy and overcome drug resistance in various cancers, including oral squamous cell carcinoma (OSCC), ovarian cancer, colon cancer, and cervical cancer. Mechanistically, quercetin appears to sensitize tumor cells to cisplatin-induced apoptosis by modulating multiple signaling pathways such as NF-κB inhibition, downregulation of anti-apoptotic proteins (e.g., xIAP), activation of caspase-8 and caspase-9 (extrinsic/intrinsic apoptosis), cell cycle arrest at G2/M phase, suppression of PI3K-Akt signaling, reduction in expression of EGFR/MYC/CCND1/ERBB2/IL6/VEGFA/PPARG oncogenic factors, and modulation of p53/HIF-1 pathways. The combination has shown synergistic effects on tumor cell death both in vitro and in vivo but is not currently approved for clinical use[1][2][3][4][5].
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