Methods and compositions for predicting therapeutic efficacy of kinase inhibitors in patients with myelodysplastic syndrome or related disorders
AssigneesOnconova Therapeutics, Inc., The Trustees of Columbia Unviersity in the City of New York
InventorsBENJAMIN TYCKO, AZRA RAZA, FRANCOIS WILHELM
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Abstract
The invention discloses a diagnostic method for predicting the therapeutic efficacy of a broad specificity kinase inhibitor in a subject with refractory cancer comprising determining the locus-specific DNA methylation profile of the subject, wherein the locus-specific DNA methylation profile predicts the therapeutic efficacy of a broad specificity kinase inhibitor for treatment of a subject with refractory cancer.
Claims22
A diagnostic method for predicting the therapeutic efficacy of a broad specificity kinase inhibitor in a subject with refractory cancer comprising:
- (a) obtaining a test genomic DNA sample from a tissue of the subject;
- (b) analyzing the DNA methylation profile of the test genomic DNA sample;
- and (c) comparing the DNA methylation profile of the one or more CpG dinucleotide sequences of the test genomic DNA sample with corresponding sequences of a discrete panel of DNA methylation profile biomarkers comprising one or more genes of the differentially methylated genes listed in Tables 1, 2, 3, or 4, or any sub-combination thereof to determine the locus specific DNA methylation profile pattern of the test genomic DNA sample in order to predict the therapeutic efficacy of a broad specificity kinase inhibitor for treatment of a subject with refractory cancer.
A method for treating a subject with refractory cancer comprising:
- (a) obtaining a test genomic DNA sample from a tissue of the subject;
- (b) analyzing the DNA methylation profile of the test genomic DNA sample;
- (c) comparing the DNA methylation profile of the one or more CpG dinucleotide sequences of the test genomic DNA sample with a corresponding sequences of a discrete panel of DNA methylation profile biomarkers comprising one or more of the differentially methylated genes listed in Tables 1, 2, 3, or 4, or any sub-combination thereof to determine a locus specific DNA methylation profile of the test genomic DNA sample to predict the therapeutic efficacy of a broad specificity kinase inhibitor for treatment of the subject with refractory cancer in advance;
- and (d) treating the subject with the broad specificity kinase inhibitor.
A test kit for predicting the therapeutic efficacy of a broad specificity kinase inhibitor in a subject with refractory cancer comprising ingredients and assays for determining the DNA methylation profile of a test genomic DNA sample and comparing the DNA methylation profile of the one or more CpG dinucleotide sequences of the test genomic DNA sample with the corresponding sequences of a discrete panel of DNA methylation biomarkers comprising one or more of the differentially methylated genes listed Tables 1, 2, 3, or 4, or any sub-combination thereof, wherein the locus-specific DNA methylation profile predicts the therapeutic efficacy of a broad specificity kinase inhibitor for treatment of a subject with refractory cancer.
Dependencies are inferred from the claim text.