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• W4213271487 abstract "Hand-foot skin reaction (HFSR) is the most debilitating and prevalent side effect caused by multikinase inhibitors (MKIs) that share vascular endothelial growth factor receptor (VEGFR) as the common inhibition target, such as sorafenib, regorafenib, axitinib, etc. Though not life-threatening, HFSR can significantly deteriorate patients' quality of life and jeopardize the continuity of cancer therapy. Despite years of efforts, there are no FDA-approved treatments for HFSR and the understanding of the precise pathogenic mechanism is still limited. In this study, we hypothesized that nitric oxide has the potential therapeutic effect to reverse the toxicity caused by MKI through upregulation of several VEGF/VEGFR downstream signaling pathways. We found that glyceryl trinitrate (GTN), a nitric oxide donor, could stimulate cell proliferation, migration, and protect cells from apoptosis induced by MKIs in vitro. Local application of GTN mitigated tissue damage in a rat model, while not impacting the anti-tumor effect of the MKI in HepG2 tumor-bearing mice. Finally, GTN ointment alleviated cutaneous damages and improved quality of life in 6 HFSR patients. Our study proposed and validated the mechanism to counteract VEGFR inhibition, providing GTN as the potential treatment to MKI-induced HFSR, which may further improve the therapeutic window of various MKI based cancer therapies." @default.
• W4213271487 created "2022-02-24" @default.
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• W4213271487 date "2022-02-01" @default.
• W4213271487 modified "2023-09-24" @default.
• W4213271487 title "Nitric Oxide in Multikinase Inhibitor-induced Hand-Foot Skin Reaction" @default.
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• W4213271487 doi "https://doi.org/10.1016/j.trsl.2022.02.004" @default.
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• W4213271487 hasPublicationYear "2022" @default.
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