Combination therapy of lymphoma

Abstract

The present disclosure provides for methods and compositions for treating cancer. A subject having lymphoma is administered an EZH2 inhibitor and an HDAC inhibitor. The combination of the EZH2 inhibitor and the HDAC inhibitor produces a synergistic effect on the cancer compared to the effect of the EZH2 inhibitor or the HDAC inhibitor alone.

1 . A method of treating lymphoma in a subject, the method comprising administering an Enhancer of Zeste Homolog 2 (EZH2) inhibitor and a histone deacetyltransferace (HDAC) inhibitor to the subject. 
     
     
         2 . The method of  claim 1 , wherein the lymphoma is an EZH2-dysregulated lymphoma. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the EZH2 inhibitor is selected from the group consisting of GSK126, tazemetostat, EPZ-011989, CPI-1205, and combinations thereof. 
     
     
         5 . The method of  claim 1 , wherein the HDAC inhibitor is selected from the group consisting of romidepsin, vorinostat, belinostat, panobinostat, and combinations thereof. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the EZH2 inhibitor and the HDAC inhibitor are administered simultaneously, sequentially or separately. 
     
     
         8 .- 9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the administration of the EZH2 inhibitor and the HDAC inhibitor produces a synergistic effect on the lymphoma compared to an effect of the EZH2 inhibitor alone or an effect of the HDAC inhibitor alone. 
     
     
         11 . The method of  claim 10 , wherein the administration of the EZH2 inhibitor and the HDAC inhibitor results in a synergistic increase in apoptosis of cancer cells and/or a synergistic reduction in tumor volume. 
     
     
         12 .- 13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the EZH2 inhibitor and/or the HDAC inhibitor are administered orally, intravenously, intramuscularly, topically, arterially, or subcutaneously. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein the subject is a human. 
     
     
         17 . The method of  claim 1 , wherein the subject tests positive for an EZH2 gene mutation. 
     
     
         18 . The method of  claim 17 , wherein the EZH2 gene mutation results in EZH2 overexpression. 
     
     
         19 . The method of  claim 2 , wherein the EZH2-dysregulated lymphoma comprises a gain-of-function mutation in an EZH2 gene. 
     
     
         20 . The method of  claim 2 , wherein the EZH2-dysregulated lymphoma is germinal center (GC) derived lymphoma. 
     
     
         21 . The method of  claim 2 , wherein the EZH2-dysregulated lymphoma is germinal center (GC) diffuse large B-cell lymphoma (GC-DLBCL), or adult T-cell leukemia lymphoma (ATLL). 
     
     
         22 . The method of  claim 1 , wherein the lymphoma is diffuse large B-cell lymphoma (DLBCL) or activated B-Cell (ABC) diffuse large B-cell lymphoma (ABC-DLBCL). 
     
     
         23 .- 24 . (canceled) 
     
     
         25 . The method of  claim 1 , wherein the lymphoma is relapsed or refractory lymphoma, B-cell lymphoma, T-cell lymphoma, GC-derived B-cell lymphoma, follicular lymphoma (FL), mantle cell lymphoma (MCL), mutant follicular lymphoma, and/or double-hit lymphoma. 
     
     
         26 .- 27 . (canceled) 
     
     
         28 . A method of treating lymphoma cells, the method comprising contacting the lymphoma cells with an EZH2 inhibitor and an HDAC inhibitor. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 28 , wherein the EZH2 inhibitor is selected from the group consisting of GSK126, tazemetostat, EPZ-011989, CPI-1205, and combinations thereof. 
     
     
         31 . The method of  claim 28 , wherein the HDAC inhibitor is selected from the group consisting of romidepsin, vorinostat, belinostat, panobinostat, and combinations thereof. 
     
     
         32 .- 35 . (canceled) 
     
     
         36 . The method of  claim 1 , further comprising administering to the subject a BCL2 inhibitor. 
     
     
         37 .- 42 . (canceled)