Markers associated with human double minute 2 inhibitors

Abstract

The invention provides methods of monitoring differential gene expression of biomarkers to determine patient sensitivity to Human Double Minute inhibitors (MDM2i), methods of determining the sensitivity of a cell to an MDM2i by measuring biomarkers and methods of screening for candidate MDM2i.

1 . A method of predicting the sensitivity of a cancer patient for treatment with a Human Double Minute 2 inhibitor (MDM2i), the method comprising:
 a) measuring differential gene expression of at least one biomarker selected from Table 2 in a cancer sample obtained from the patient; and   b) comparing the differential gene expression of the at least one biomarker with gene expression of said biomarker in a control sample, wherein the increase or decrease in gene expression comparison indicates that the patient is sensitive to treatment with an MDM2i.   
     
     
         2 . The method of  claim 1 , wherein more than one biomarker is selected from Table 2. 
     
     
         3 . The method of  claim 1 , comprising the biomarkers MDM2, CDKN1A, ZMAT3, DDB2, FDXR, RPS27L, BAX, RRM2B, SESN1, CCNG1, XPC, TNFRSF10B and AEN. 
     
     
         4 . The method of  claim 1 , wherein comparing the differential gene expression of the at least one biomarker with gene expression of a control sample indicates a functional p53 gene pathway. 
     
     
         5 . The method of  claim 1 , wherein the cancer sample is selected from the group consisting of breast, lung, pancreas, ovary, central nervous system (CNS), endometrium, stomach, large intestine, colon, esophagus, bone, urinary tract, hematopoietic, lymphoid, liver, skin, melanoma, kidney, soft tissue sarcoma and pleura. 
     
     
         6 . The method of  claim 1 , wherein a nucleic acid or protein of at least one biomarker is measured. 
     
     
         7 . The method of  claim 1 , wherein the expression of the at least one biomarker is increased in the cancer sample when compared to a control sample. 
     
     
         8 . The method of  claim 1 , wherein the MDM2i is selected from Table 1. 
     
     
         9 .- 16 . (canceled) 
     
     
         17 . A method of predicting the sensitivity of a cancer cell to a Human Double Minute 2 inhibitor (MDM2i), the method comprising:
 a) obtaining a cancer sample from a cancer patient,   b) measuring differential gene expression of at least two biomarkers selected from Table 2 in the cell; and   c) comparing the differential gene expression of the at least two biomarkers selected from Table 2 with gene expression of the at least two biomarkers from a normal or control cell.   
     
     
         18 . The method of  claim 17 , wherein the MDM2i is selected from Table 1. 
     
     
         19 . The method of  claim 17 , wherein more than three biomarkers are selected from Table 2. 
     
     
         20 . The method of  claim 17 , comprising the biomarkers MDM2, CDKN1A, ZMAT3, DDB2, FDXR, RPS27L, BAX, RRM2B, SESN1, CCNG1, XPC, TNFRSF10B and AEN. 
     
     
         21 . The method of  claim 17 , wherein comparing the differential gene expression of the at least two biomarkers with gene expression of a control sample indicates a functional p53 gene pathway. 
     
     
         22 . The method of  claim 17 , wherein the cancer sample is selected from the group consisting of breast, lung, pancreas, ovary, central nervous system (CNS), endometrium, stomach, large intestine, colon, esophagus, bone, urinary tract, hematopoietic, lymphoid, liver, skin, melanoma, kidney, soft tissue sarcoma and pleura. 
     
     
         23 . The method of  claim 17 , wherein a nucleic acid or protein of at least two biomarkers is measured. 
     
     
         24 . The method of  claim 17 , wherein the gene expression of the at least two biomarkers is increased in the cancer cell. 
     
     
         25 .- 48 . (canceled)