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Methods for predicting tumor response to DNA methylation inhibitors and alternative treatment regimens to overcome resistance
Methods for predicting tumor response to DNA methylation inhibitors and alternative treatment regimens to overcome resistance
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机译:预测肿瘤对DNA甲基化抑制剂反应的方法和克服耐药性的替代治疗方案
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摘要
The present invention provides a method for predicting the sensitivity of a patient suffering from a cancer disease to DNA methylation inhibitor therapy, which comprises determining in vitro in cancer cells taken from the patient and comparing with values for parent type of cells - the level of expression of at least one bromodomain containing gene, and/or - the level of expression of at least one bromodomain containing protein and/or - the mutations involving the non-synonymous change in amino acid sequence of at least one bromodomain containing gene and/or - the half maximal inhibitory concentration (IC 50 ) of a DNA methylation inhibitor and/or a histone demethylase inhibitor, wherein the increase in the half maximal inhibitory concentration of the DNA methylation inhibitor and/or the histone demethylase inhibitor signifies cross-resistance, and/or - the half maximal inhibitory concentration (IC 50 ) of a selective BET bromodomain inhibitor, wherein the decrease in the half maximal inhibitory concentration of the selective BET bromodomain inhibitor signifies sensitivity. The invention further provides a combination therapy of cancers using bromodomain inhibitors in combination with DNA methylation inhibitors.
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