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On April 21, Nature Cancer published online the title of Therapeutic targeting of the mevalonate–geranylgeranyl diphosphate pathway with statins overcomes chemotherapy resistance in small cell by Ji Hongbin's research group of the Center for Excellence in Molecular and Cell Science (Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences Research results of lung cancer
This study revealed the function and mechanism of mevalonate (MVA)-geranylgeranyl diphosphate (GGPP) metabolic pathway in chemoresistance in small cell lung cancer, and proposed a new strategy for targeted therapy
The function and mechanism of mevalonate (MVA)-geranylgeranyl diphosphate (GGPP) metabolic pathway in chemoresistance of small cell lung cancer were revealed, and a new targeted therapy strategy was proposed
Small cell lung cancer accounts for about 15% of lung cancers and is the subtype with the highest degree of malignancy and the worst prognosis among all lung cancer subtypes
In this study, by establishing xenografts (PDX) derived from small cell lung cancer patient samples and xenograft mouse models derived from human small cell lung cancer cell lines, the mouse models were treated with chemotherapy for up to one and a half years by simulating the clinical dosing regimen.
Using a series of PDX models of acquired and primary resistance, the researchers further searched for tumor markers that responded better to statin therapy
In summary, this study revealed the important role of mevalonate metabolism in the chemoresistance of small cell lung cancer by establishing and studying a mouse model of small cell lung cancer chemotherapy resistance, and proposed that statins can be used to target MVA-GGPP metabolic pathway as a strategy to overcome chemoresistance in small cell lung cancer for later-line clinical treatment
The research work is supported by the Animal Experiment Technology Platform, Chemical Biology Platform, Cell Biology Platform and Molecular Biology Platform of the Public Technology Service Center of the Center of Excellence for Molecular Cells.
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