Melanoma is the most life-threatening form of skin cancer. More than 50% of melanoma patients carry BRAFV600E mutation, but most patients develop resistance, side effects, and relapse after treatment with BRAFV600E inhibitor drugs such as vemurafenib. Dr. Lie-Fen Shyur’s team at the Agricultural Biotechnology Research Center discovered that sesquiterpene lactone deoxyelephantopin (DET) and its structurally modified derivative DETD-35 are novel GPX4 inhibitors and ferroptosis inducers through which vemurafenib induced abnormal primary and lipid metabolisms in resistant melanoma were reversed; in turn, vemurafenib drug sensitivity to resistant melanoma was enhanced. DET and DETD-35 show great potential as BRAFV600E inhibitor drug adjuvants against melanoma. This study was published in Pharmacological Research.

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Phyto-sesquiterpene lactones DET and DETD-35 induce ferroptosis in vemurafenib sensitive and resistant melanoma via GPX4 inhibition and metabolic reprogramming