Method for treating prostate cancer
The invention provides a method for treating prostate cancer in a subject comprising administering to the subject an effective amount of a selective inhibitor of one or more of CDK8 and CDK19. In some embodiments the inhibitor inhibits CDK19. In some embodiments, the inhibitor inhibits CDK8 at a Kd of lower than 200 nM and/or inhibits CDK19 at a Kd of lower than 100 nM. In some embodiments, the prostate cancer is androgen independent. In some embodiments, the prostate cancer is androgen independent due to one or more of androgen receptor gene amplification, androgen receptor gene mutation, ligand-independent transactivation of androgen receptor and activation of intracellular androgen synthesis. In some embodiments, the inhibitor inhibits increased activity of NF-κB. In some embodiments, the inhibitor does not inhibit increased basal levels of NF-κB. In some embodiments, inhibition of one or more genes by AR is not inhibited.
1. A method for treating prostate cancer in a subject comprising administering to the subject an effective amount of a selective inhibitor of one or more of CDK8 and CDK19, wherein the prostate cancer is androgen independent and wherein said inhibitor inhibits increased activity of NF-κB.
2. The method according to claim 1 , wherein the selective inhibitor of one or more of CDK8 or CDK19 is selected from Senexin A, Senexin B and combinations thereof.
3. The method according to claim 2 , wherein the inhibitor inhibits CDK19.
4. The method according to claim 2 , wherein the inhibitor inhibits CDK8.
5. The method according to claim 2 , wherein the inhibitor inhibits CDK8 and CDK19.
6. The method according to claim 2 , wherein the prostate cancer is androgen independent due to one or more of androgen receptor gene amplification, androgen receptor gene mutation, ligand-independent transactivation of androgen receptor and activation of intracellular androgen synthesis.