Abstract: The invention provides DNA damage response (DDR) pathway genes and their gene products as biomarkers to predict effective treatment of cancer using an MDM2 antagonist. Identifying one or more DDR pathway biomarkers in a cancer patient allows a determination to be made whether the patient's cancer is likely to be successfully treated using an MDM2 antagonist. Accordingly, the invention relates generally to a companion diagnostic for MDM2 antagonist therapy.

Abstract: The invention provides biomarkers to predict effective treatment of cancer using an MDM2 antagonist. Identifying one or more of these biomarkers in a cancer patient allows a determination to be made whether the patient's cancer is likely to be successfully treated using an MDM2 antagonist. Accordingly, the invention relates generally to a companion diagnostic for MDM2 antagonist therapy. The biomarkers are: (i) BAP1; and/or (ii) CDKN2A; and/or (iii) one, two, three, four, five, six, seven, eight, nine, ten or more of: CXCL10, CXCL11, RSAD2, MX1, BATF2, IF144L, IFITM1, ISG15, CMPK2, IF127, CD74, IFIH1, CCRL2, IF144, HERC6, ISG20, IFIT3, HLA-C, OAS1, IF135, IRF9, EPSTI1, USP18, BST2, CSF1, C1S, DHX58, TRIM14, OASL, IRF7, LGALS3BP, DDX60, LAP3, LAMP3, PARP12, PARP9, SP110, PLSCR1, WARS, STAT1, IRF3, IRF5, MSC, JUN, SPI1, IRF1, COMMD3-BMI1, STAT2, RUNX3, SREBF1, FLI1 and BRCA1.

Abstract: The invention provides SKP2 as a biomarker to predict effective treatment of cancer using an MDM2 antagonist. Identifying this biomarker in a cancer patient allows a determination to be made whether the patient's cancer is likely to be successfully treated using an MDM2 antagonist. Accordingly, the invention relates generally to a companion diagnostic for MDM2 antagonist therapy. The SKP2 biomarker may be measured directly, or indirectly by detection of a molecule that is functionally upstream or downstream of SKP2 and the level of which correlates with the level of the SKP2 biomarker, such as the detection of one or more SKP2 substrates.