Anti-tumor therapy

Abstract

Panels, compositions, and methods for treating cancer in a subject in need thereof are disclosed involving one or more genes the suppression of which renders the cancer chemosensitive and/or radiosensitive.

We claim: 
     
         1 . A panel for treating a cancer in a subject in need thereof, the panel comprising:
 one or more genes contributing to tumor development or chemoresistance and/or radioresistance of a cancer cell,   wherein suppression of the one or more genes results in at least one of: suppression of growth or proliferation of the cancer cell, cell death of the cancer cell, or sensitization of the cancer cell to chemotherapy and/or radiotherapy.   
     
     
         2 . The panel of  claim 1 , wherein the cancer is at least one of Jak/Stat dependent or associated with activation of a Jak/Stat-related pathway;
 wherein the Jak comprises a Jak-1, a Jak-2, a Jak-3 or a Tyk2 kinase, and the Stat comprises a Stat1, a Stat2, a Stat 3, a Stat4, a Stat5, or a Stat6 transcriptional factor.   
     
     
         3 . The panel of  claim 2 , wherein the one or more genes is an interferon stimulated gene. 
     
     
         4 . The panel of  claim 3 , wherein the one or more genes is selected from the group consisting of DHX58 (LGP2), PLSCR1, USP18, PSMB10, IFITM1, OASL, EPSTL1, LGALS3BP, IFIH1, ABCC3, DTX3L, PSMB9, IRF9, TAGLN, IFIT2, TPD52L1, CXCL9, GBP1, BST2, SP110, HERC5, CCL2, WARS, MCL1, and TRIM14. 
     
     
         5 . The panel of  claim 1 , wherein the one or more genes contributes to chemoresistance and/or radioresistance of the cancer cell. 
     
     
         6 . A panel for treating a cancer in a subject in need thereof, the panel comprising:
 one or more inhibitors of expression and/or functional activity specific for one or more genes selected from the group consisting of DHX58, PLSCR1, USP18, PSMB10, IFITM1, OASL, EPSTL1, LGALS3BP, IFIH1, ABCC3, DTX3L, PSMB9, IRF9, TAGLN, IFIT2, TPD52L1, CXCL9, GBP1, BST2, SP110, HERC5, CCL2, WARS, MCL1, and TRIM14,   wherein administration of the one or more inhibitors of expression to a cancer cell results in at least one of: suppression of growth or proliferation of the cancer cell, cell death of the cancer cell, or sensitization of the cancer cell to chemotherapy and/or radiotherapy.   
     
     
         7 . The panel of  claim 6 , wherein the one or more inhibitors of expression and/or functional activity comprises an siRNA molecule, an shRNA molecule, a micro-RNA molecule, a small molecule, a peptide inhibitor, or a combination or a pharmaceutically acceptable salt or prodrug thereof, and
 wherein the one or more inhibitors of expression and/or functional activity is in a therapeutically effective amount and formulated for administration to the subject.   
     
     
         8 . The panel of  claim 7 , wherein the panel comprises inhibitors of expression and/or functional activity specific for at least two genes selected from the group consisting of DHX58, PLSCR1, USP18, PSMB10, IFITM1, OASL, EPSTL1, LGALS3BP, IFIH1, ABCC3, DTX3L, PSMB9, IRF9, TAGLN, IFIT2, TPD52L1, CXCL9, GBP1, BST2, SP110, HERC5, CCL2, WARS, MCL1, and TRIM14. 
     
     
         9 . The panel of  claim 6 , wherein administration to the subject of one or more antineoplastic agents and radio therapy results in at least one of: suppression of growth or proliferation of the cancer cell, or cell death of the cancer cell;
 wherein the administration of the one or more antineoplastic agents or radio therapy is subsequent to the administration of the inhibitor of expression and/or functional activity.   
     
     
         10 . A kit for treating cancer in a subject in need thereof, comprising:
 a panel comprising one or more inhibitors of expression and/or functional activity specific for one or more genes selected from the group consisting of DHX58, PLSCR1, USP18, PSMB10, IFITM1, OASL, EPSTL1, LGALS3BP, IFIH1, ABCC3, DTX3L, PSMB9, IRF9, TAGLN, IFIT2, TPD52L1, CXCL9, GBP1, BST2, SP110, HERC5, CCL2, WARS, MCL1, and TRIM14; and   an optional antineoplastic agent.   
     
     
         11 . The kit of  claim 10  further comprising at least one of a Jak2 or a Jak1/Jak2 inhibitor in a therapeutically effective amount. 
     
     
         12 . The kit of  claim 11 , wherein the Jak2 inhibitor is SAR302503. 
     
     
         13 . The kit of  claim 11 , wherein the Jak1/Jak2 inhibitor is Ruxolitinib. 
     
     
         14 . A pharmaceutical composition, comprising:
 a therapeutically effective amount of an agent that suppresses at least one gene in a subject, the gene selected from the group consisting of DHX58, PLSCR1, USP18, PSMB10, IFITM1, OASL, EPSTL1, LGALS3BP, IFIH1, ABCC3, DTX3L, PSMB9, IRF9, TAGLN, IFIT2, TPD52L1, CXCL9, GBP1, BST2, SP110, HERC5, CCL2, WARS, MCL1, and TRIM14; and   one or more pharmaceutically acceptable carriers, diluents and excipients.   
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the composition further comprises a therapeutically effective amount of at least one of an antineoplastic agent or a radiotherapy agent. 
     
     
         16 . The pharmaceutical composition of  claim 15 , wherein the pharmaceutical composition is formulated to be administered to the subject in at least one of an oral, inhalation, parental injection, topical, or suppository dosage form. 
     
     
         17 . A method of treating a cancer in a subject by increasing the sensitivity of tumor cells of the subject to radiotherapy, comprising:
 a) administering to the tumor cells a siRNA or shRNA to directly target PSMB9 mRNA in an amount that is sufficient to suppress expression of PSMB9 gene, thereby increasing the sensitivity of the cells to radiotherapy; and   b) administration to the subject a therapeutically effective amount of at least one of an antineoplastic agent or radiotherapy.   
     
     
         18 . The method of  claim 17  further comprising administration to the subject a therapeutically effective amount of at least one of a Jak2 or a Jak1/Jak2 inhibitor. 
     
     
         19 . The method of  claim 18 , wherein the PSMB9 mRNA is decreased by at least 25% in tumor cells compared to untreated cells of the same tumor cells. 
     
     
         20 . The method of  claim 18 , wherein the radio therapy comprises at least one of brachytherapy, external beam radiation therapy, or radiation from cesium, iridium, iodine, or cobalt. 
     
     
         21 . The method of  claim 17  further comprises administrating to the tumor cells a siRNA or shRNA to directly target mRNA of a gene selected from the group consisting of DHX58, PLSCR1, USP18, PSMB10, IFITM1, OASL, EPSTL1, LGALS3BP, IFIH1, ABCC3, DTX3L, IRF9, TAGLN, IFIT2, TPD52L1, CXCL9, GBP1, BST2, SP110, HERC5, CCL2, WARS, MCL1, and TRIM14.