Method of predicting the tumor response to DNA methylation inhibitors and alternative therapeutic regimens for overcoming resistance

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.