Treatments and diagnostics for cancers

Abstract

Treatments and diagnostics for treatment efficacy against solid and liquid cancers are described. The treatments utilize a combination therapy of Galeterone and a proteasome inhibitor. The diagnostics can measure androgen receptor (AR) cleavage products including AR-variant 7 (AR-V7) cleavage products, Poly (ADP-ribose) polymerase (PARP) cleavage products, and/or Spectrin α2 cleavage products or inhibition of DUB activities from a blood sample to monitor treatment efficacy for castration-resistant prostate cancer (CRPC) or multiple myeloma (MM).

What is claimed is: 
     
         1 . A method of providing an anti-cancer effect in a subject having a solid tumor cancer or a liquid cancer, comprising administering a therapeutically effective amount of Galeterone and a therapeutically effective amount of a proteasome inhibitor to the subject, thereby providing an anti-cancer effect in the subject. 
     
     
         2 . The method of  claim 1 , wherein Galeterone has the structure 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , wherein the proteasome inhibitor is selected from β-lapachone, bortezomib, bortesamide, carfilzomib, CEP-18770, disulfiram, epigallocatechin-3-gallate, epoxomicin, lactacystin, laxomib (MLN9708), MG132, MLN9708, oprozomib (ONX 0912), salinosporamide A (NPI-0052, marizomib), or an immunoproteasome inhibitor. 
     
     
         4 . The method of  claim 3 , wherein the proteasome inhibitor is bortezomib. 
     
     
         5 . The method of  claim 1 , wherein the proteasome inhibitor potentiates the anti-cancer effect of Galeterone. 
     
     
         6 . The method of  claim 5 , wherein the subject has castration-resistant prostate cancer (CRPC) or multiple myeloma (MM). 
     
     
         7 . The method of  claim 1 , wherein the subject has castration-resistant prostate cancer (CRPC) or multiple myeloma (MM). 
     
     
         8 . A composition comprising a therapeutically effective amount of Galeterone and a therapeutically effective amount of a proteasome inhibitor for use in the method of  claim 1 . 
     
     
         9 . The composition of  claim 8 , wherein the proteasome inhibitor comprises one or more of β-lapachone, bortezomib, bortesamide, carfilzomib, CEP-18770, disulfiram, epigallocatechin-3-gallate, epoxomicin, lactacystin, laxomib (MLN9708), MG132, MLN9708, oprozomib (ONX 0912), salinosporamide A (NPI-0052, marizomib), or an immunoproteasome inhibitor. 
     
     
         10 . The method of  claim 9 , wherein the proteasome inhibitor is bortezomib. 
     
     
         11 . A method to target one or more deubiquitinating enzymes (DUBs), comprising administering a therapeutically effective amount of Galeterone in vivo or in vitro, thereby targeting DUBs. 
     
     
         12 . The method of  claim 11 , wherein the targeting provides an anti-cancer effect. 
     
     
         13 . The method of  claim 11 , further comprising administering a therapeutically effective amount of a proteasome inhibitor. 
     
     
         14 . The method of  claim 13 , wherein the proteasome inhibitor comprises one or more of β-lapachone, bortezomib, bortesamide, carfilzomib, CEP-18770, disulfiram, epigallocatechin-3-gallate, epoxomicin, lactacystin, laxomib (MLN9708), MG132, MLN9708, oprozomib (ONX 0912), salinosporamide A (NPI-0052, marizomib), or an immunoproteasome inhibitor. 
     
     
         15 . The method of  claim 14 , wherein the proteasome inhibitor is bortezomib. 
     
     
         16 . The method of  claim 12 , wherein the DUBs are in solid and/or liquid tumors, and the therapeutically effective amount of Galeterone is administered to a subject in need thereof. 
     
     
         17 . The method of  claim 11 , which is a method to target 19S proteasome-associated DUBs and 20s proteasome, further comprising administering a therapeutically effective amount of a proteasome inhibitor in vivo or in vitro.