P53 modulator and cancer target

Abstract

Methods of screening for modulators of TRIM24 (also known as TIF1-ALPHA) expression and/or biological activity are described. In particular, methods of screening for modulators of TRIM24 E3 ligase activity, and specifically an E3 ligase activity directed at p53 as the target polypeptide are also described. Modulators of TRIM24 expression and activity are provided and their use in treatment of cancer, particularly in breast, colon, prostate, renal cancers and in acute lymphoblastic leukemia. Suitable modulators of TRIM24 expression include siRNA and shRNA and can be used in the treatment of cancer and for targeting cancer stem cells.

1 .- 44 . (canceled) 
     
     
         45 . A method of treating cancer in a patient in need thereof, comprising administering to a patient in need thereof an effective amount of an inhibitor of TRIM24, which inhibitor comprises a moiety selected from: a polynucleotide that is substantially complementary to a TRIM24 polynucleotide sequence; an oligonucleotide that is substantially complementary to at least 12 contiguous bases of a TRIM24 polynucleotide sequence; an oligonucleotide RNAi molecule that is substantially complementary to at least 19 contiguous bases of a TRIM24 sequence; an antibody; a small molecule; an artificial transcription factor; a glycoprotein; and a polysaccharide. 
     
     
         46 . The method of  claim 45 , wherein the inhibitor of TRIM24 comprises an siRNA or shRNA molecule that targets at least 19 contiguous bases of SEQ ID NOs: 1 and/or 59-64. 
     
     
         47 . The method of  claim 45 , wherein the cancer is selected from one or more of: breast cancer; retinal cancer; prostate cancer; colon cancer; and acute lymphoblastic leukaemia. 
     
     
         48 . The method of  claim 46 , wherein the cancer is selected from one or more of: breast cancer; retinal cancer; prostate cancer; colon cancer; and acute lymphoblastic leukaemia.