Combination methods for treatment of disease
View Patent ↗In some aspects, the invention provides compositions and methods of use for treating a variety of diseases. In some aspect, the compositions and methods involve combined modulation of transcriptional modulators.
1. A method of inhibiting proliferation or survival of a cell comprising contacting the cell with a positive transcription elongation factor b (P-TEFb) inhibitor and a c-Myc inhibitor.
2. The method of claim 1 , wherein the P-TEFb inhibitor is a CDK9 inhibitor.
3. The method of claim 1 , wherein the P-TEFb inhibitor is flavopiridol or a flavopiridol analog.
4. The method of claim 1 , wherein the c-Myc inhibitor is a compound that inhibits interaction between c-Myc and Max.
5. The method of claim 1 , wherein the cell is a human cell.
6. The method of claim 1 , wherein the cell is a tumor cell.
7. The method of claim 1 , wherein the cell is a stem cell.
8. A method of inhibiting pause release at a plurality of Myc target genes in a cell comprising contacting the cell with a positive transcription elongation factor b (P-TEFb) inhibitor and a c-Myc inhibitor.
9. The method of claim 8 , wherein the cell is contacted with a P-TEFb inhibitor at a concentration that does not substantially inhibit pause release at non-c-Myc target genes when contacted with the cell in the absence of a c-Myc inhibitor.
10. A method of treating a subject suffering from a proliferative disease comprising administering therapeutically effective amounts of a positive transcription elongation factor b (P-TEFb) inhibitor and a c-Myc inhibitor to the subject.
11. The method of claim 10 , wherein the proliferative disease is a tumor.
12. The method of claim 10 , wherein the P-TEFb inhibitor is administered at a reduced dose relative to a standard dosing regimen.
13. The method of claim 10 , wherein the subject is a human.
14. A composition comprising a positive transcription elongation factor b (P-TEFb) inhibitor and a c-Myc inhibitor.
15. A method for testing the ability of a compound combination to inhibit cell survival or proliferation, comprising (a) contacting one or more test cells with a positive transcription elongation factor b (P-TEFb) inhibitor and a c-Myc inhibitor; and (b) assessing survival or proliferation of the one or more test cells.
16. A method of modifying cell state or cell type comprising contacting the cell with a c-Myc inhibitor and a modulator of a second transcription modulator.
17. The method of claim 16 , wherein cell state is proliferation state.
18. The method of claim 16 , comprising inhibiting proliferation or survival of a cell.
19. The method of claim 16 , comprising contacting the cell with a P-TEFb inhibitor and a c-Myc inhibitor, whereby cell proliferation or survival is inhibited.
20. A method of modulating pause release at a plurality of c-Myc target genes in a cell comprising contacting the cell with a c-Myc modulator and a modifier of a second transcriptional modulator.
21. A method of treating a subject suffering from a proliferative disease comprising administering therapeutically effective amounts of a positive transcription elongation factor b (P-TEFb) inhibitor and an NF-kB inhibitor to the subject.
22. A method of modulating pause release at a plurality of NF-kB target genes in a cell comprising contacting the cell with an NF-kB modulator and a modifier of a second transcriptional modulator.
23. The method of claim 8 , wherein the P-TEFb inhibitor is a CDK9 inhibitor.
24. The method of claim 8 , wherein the P-TEFb inhibitor is flavopiridol or a flavopiridol analog.
25. The method of claim 8 , wherein the cell is a human cell.
26. The method of claim 8 , wherein the cell is a tumor cell.
27. The method of claim 8 , wherein the cell is a stem cell.
28. The method of claim 10 , wherein the P-TEFb inhibitor is a CDK9 inhibitor.
29. The method of claim 10 , wherein the P-TEFb inhibitor is flavopiridol or a flavopiridol analog.
30. The composition of claim 14 , wherein the P-TEFb inhibitor is a CDK9 inhibitor.
31. The composition of claim 14 , wherein the P-TEFb inhibitor is flavopiridol or a flavopiridol analog.
32. The method of claim 20 , wherein the second transcriptional modulator is P-TEFb.
33. The method of claim 22 , wherein the second transcriptional modulator is P-TEFb.