Method for treating cancer
View Patent ↗The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.
1. A method comprising contacting a human cancer cell with an amount of an EZH2 inhibitor effective for increasing expression of a major histocompatibility complex (MHC) in the cancer cell, wherein (1) the cancer cell comprises a chromosomal translocation t(x;18)(p11.2;q11.2) that causes a SS18-SSX fusion gene; or (2) the function and/or expression of INI1 is reduced in the cancer cell; or (3) the cancer cell comprises aberrant, misregulated, or increased EZH2 activity.
2. The method of claim 1 , wherein the cancer cell comprises aberrant, misregulated, or increased EZH2 activity.
3. The method of claim 1 , wherein the cancer cell comprises a chromosomal translocation t(x;18)(p11.2;q11.2) that causes a SS18-SSX fusion gene.
4. The method of claim 1 , wherein the function and/or expression of INI1 is reduced in the cancer cell.
5. The method of claim 1 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound.
7. The method claim 6 , wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor.
8. The method of claim 1 , wherein the cancer cell is in a subject.
9. The method of claim 8 , wherein the subject is a human.
10. The method claim 1 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
11. The method claim 1 , wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of
12. The method claim 1 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
13. The method claim 1 , wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of
14. The method claim 1 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
15. The method claim 1 , wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of
16. The method claim 1 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
17. The method claim 1 , wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of
18. The method claim 1 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
19. The method claim 1 , wherein the EZH2 inhibitor is a pharmaceutically acceptable salt of
20. The method of claim 1 , wherein the MEC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L.
21. The method of claim 10 , wherein the MEC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L.
22. The method of claim 10 , wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound.
23. The method claim 22 , wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor.
24. The method claim 2 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
25. The method of claim 24 , wherein the MEC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L.
26. The method of claim 24 , wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound.
27. The method claim 26 , wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor.
28. The method claim 3 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
29. The method of claim 28 , wherein the MHC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L.
30. The method of claim 28 , wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound.
31. The method of claim 30 , wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor.
32. The method of claim 4 , wherein the EZH2 inhibitor is
or a pharmaceutically acceptable salt thereof.
33. The method of claim 32 , wherein the MHC is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L.
34. The method of claim 33 , wherein the method further comprises contacting the cancer cell with a chemotherapeutic compound.
35. The method claim 34 , wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor.