Method and kits for identifying of cdk9 inhibitors for the treatment of cancer

Abstract

A method of determining sensitivity to cancer treatment includes the step of determining the presence of overexpression of MYC in a biological sample from a patient suffering from cancer, wherein the presence of overexpression of MYC indicates a sensitivity to a treatment by a CDK9 inhibitor and wherein the cancer is selected from the group consisting of carcinoma, leukemia, and lymphoma.

1 . A method of determining sensitivity to cancer treatment in a patient suffering from cancer, the method comprising the steps of:
 determining the presence of overexpression of MYC in a biological sample from the patient, wherein the presence of overexpression of MYC indicates a sensitivity to a treatment by a CDK9 inhibitor,   wherein the cancer is selected from the group consisting of carcinoma, leukemia, and lymphoma.   
     
     
         2 . The method of  claim 1 , wherein the cancer is hepatocellular carcinoma. 
     
     
         3 . The method of  claim 1 , wherein the cancer is non-small cell lung carcinoma. 
     
     
         4 . The method of  claim 1 , further comprising the step of administering an effective amount of the CDK9 inhibitor into the patient if a overexpression of MYC is found in the biological sample. 
     
     
         5 . The method of  claim 4 , wherein the CDK9 inhibitor is PHA 767491, PHA-793887, PHA-848125, BAY 1143572, BAY 1112054, Cdk9 inhibitor II (CAS 140651-18-9 from Calbiochem), DRB, AZD-5438, SNS-032, dinaciclib, LY2857785, flavopiridol, purvalanol B, CDKI-71, CDKI-73, CAN508, FIT-039, CYC065, 3,4-dimethyl-5-[2-(4-piperazin-1-yl-phenylamino)-pyrimidin-4-yl]-3H-thiazol-2-one, wogonin, apigenin, chrysin, luteolin, 4-methyl-5-[2-(3-nitroanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine, shRNAs against CDK9, anti-sense mRNA against CDK9 and anti-CDK9 antibodies. 
     
     
         6 . A method of evaluating the efficacy of administering CDK9 inhibitors in a patient suffering from cancer, the method comprising the steps of:
 determining the presence in a biological sample from the patient of suppressed levels of phosphorylation of Ser2 on the C-terminal repeat domain (CTD) of RNA Pol II, wherein the presence of suppressed levels of phosphorylation of Ser2 on the CTD of RNA Pol II is indicative that CDK9 is being inhibited in the patient,   wherein the cancer is selected from the group consisting of carcinoma, leukemia, and lymphoma.   
     
     
         7 . The method of  claim 6 , wherein the cancer is hepatocellular carcinoma. 
     
     
         8 . The method of  claim 6  wherein the cancer is non-small cell lung carcinoma. 
     
     
         9 - 15 . (canceled) 
     
     
         16 . A kit for determining sensitivity to a CDK9 inhibitor in a cancer patient, comprising:
 (1) one or more synthetic oligonucleotides that specifically hybridizes to a human MYC RNA or (2) one or more antibodies that specifically bind to a human MYC protein; and   one or more reagents for processing a biological sample to obtain nucleotide molecules or proteins,   wherein the patient is suffering from a carcinoma, leukemia or lymphoma.   
     
     
         17 . The kit of  claim 16 , further comprising reagents for RNA purification or protein purification. 
     
     
         18 . The kit of  claim 16  or  17 , further comprising one or more reagents for determining levels of phosphorylation of Ser2 on the C-terminal repeat domain (CTD) of RNA Pol II. 
     
     
         19 . A kit for evaluating the efficacy of administering CDK9 inhibitors in a patient suffering from cancer, comprising:
 One or more reagents for determining a level of phosphorylation of Ser2 on the C-terminal repeat domain (CTD) of RNA Pol II in a biological sample from the patient,   one or more reagents for processing the biological sample to obtain proteins from the sample,   wherein the cancer is selected from the group consisting of carcinoma, leukemia, and lymphoma.