Biomarkers for predicting the sensitivity and response of protein kinase CK2-mediated diseases to CK2 Inhibitors
OwnerDenis DRYGIN, Sean E. O'BRIEN +7inventors
InventorsDenis DRYGIN, Sean E. O'BRIEN, Kenna L. ANDERES, Daniel VON HOFF, John K.C. LIM, Claire S. PADGETT, Joshua R. BLIESATH, Caroline B. HO, William G. Rice
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Abstract
Disclosed are biomarkers for determining the sensitivity of protein kinase CK2-mediated diseases, such as proliferative and/or inflammatory disorders, to treatment with CK2 inhibitors. These biomarkers can be used to predict or select subjects likely to be responsive to treatment with a CK2 inhibitor, and to treat or monitor subjects undergoing treatment with a CK2 inhibitor.
Claims31
A method for monitoring the response of a subject being treated with a CK2 inhibitor, said method comprising:
- (a) determining the level of a biomarker in a biological sample derived from the subject at a time point .during or after administration of the CK2 inhibitor, wherein the biomarker is selected from the level of phosphorylated Akt S129, the ratio of phosphorylated Akt S 129 to total Akt, the level of phosphorylated Akt S473, the ratio of phosphorylated Akt S 473 to total Akt, the level of phosphorylated p21 T145, the ratio of phosphorylated p21 T 145 to total p21, the level of phosphorylated NF-κB S529, the ratio of phosphorylated NF-κB S529 to total NF-κB, the level of phosphorylated STAT3 T705, the ratio of phosphorylated STAT3 T705 to total STAT3, the level of phosphorylated JAK2 Y1007/1008, and the ratio of phosphorylated JAK2 Y1007/1008 to total JAK2;
- and
- (b) comparing the level of the biomarker in the biological sample with a reference level of the biomarker;
- wherein a decrease in the level of the biomarker in the biological sample compared to the reference level of the biomarker is indicative of a positive response to treatment with said CK2 inhibitor.
A method for monitoring the response of a subject being treated with a CK2 inhibitor, said method comprising:
- (a) determining the level of mRNA and/or protein expression of a biomarker in a biological sample derived from the subject at a time point during or after administration of the CK2 inhibitor, wherein the biomarker is selected from IL-6, IL-8, CK2α, CK2α′, CK2β, VEGF, and HIF-1α;
- and
- (b) comparing the level of the biomarker in the biological sample with a reference level of the biomarker;
- wherein a decrease in the level of the biomarker in the biological sample compared to the reference level of the biomarker is indicative of a positive response to treatment with said CK2 inhibitor.
A method for predicting the clinical response of a CK2-mediated disease to treatment with a CK2 inhibitor in a subject, said method comprising determining the level of one or more biomarkers in a biological sample derived from the subject, wherein an elevated level of said one or more biomarkers relative to a control biological sample is indicative of sensitivity of the CK2-mediated disease to treatment with said CK2 inhibitor, and wherein said biomarker is selected from the level of phosphorylated Akt S129, the ratio of phosphorylated Akt S 129 to total Akt, the level of phosphorylated Akt S473, the ratio of phosphorylated Akt S 473 to total Akt, the level of phosphorylated p21 T145, the ratio of phosphorylated p21 T145 to total p21, the level of phosphorylated NF-κB S529, the ratio of phosphorylated NF-κB S529 to total NF-κB, the level of phosphorylated STAT3 T705, the ratio of phosphorylated STAT3 T705 to total STAT3, the level of phosphorylated JAK2 Y1007/1008, the ratio of phosphorylated JAK2 Y1007/1008 to total JAK2, the expression level of IL-6, the expression level of IL-8, the expression level of CK2α, the expression level of CK2α′, the expression level of CK2β, the expression level of VEGF, and the expression level of HIF-1α.
A method for predicting the clinical response of a cancer or malignancy to treatment with a CK2 inhibitor in a subject, said method comprising:
- (a) determining the level of CK2α′ mRNA and/or protein expression in a biological sample derived from the subject;
- and
- (b) determining the level of p-Akt S129 and/or the ratio of p-Akt S129 to total Akt in a biological sample derived from the subject;
- wherein a positive correlation between the level of CK2α′ mRNA and/or protein expression and the level of p-Akt S129 and/or ratio of p-Akt S129 to total Akt is indicative of sensitivity of the cancer or malignancy to treatment with said. CK2 inhibitor.
Dependencies are inferred from the claim text.