Methods of screening for modulators of TRIM24 (also known as TIF1 -ALPHA) expression and/or biological activity are described. In particular, methods of screening 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 leukaemia. Suitable modulators of TRIM24 expression include siRNA and shRNA and can be used in the treatment of cancer and for targeting cancer stem cells.