Treatment of cancer with bio and chemotherapy

Abstract

This invention relates to compositions and methods utilizing a chemotherapeutic drug and 6-bromoindirubin3′-oxime (BIO) for the treatment of cancer, including glioblastoma multiforme. The present invention demonstrates that BIO works synergistically with chemotherapeutic drugs to increase the cytotoxic effects of these drugs in glioma cells.

1 . A method for treating cancer in a subject in need thereof, comprising:
 providing a glycogen synthase kinase-3 (“GSK-3”) antagonist and/or Wnt canonical pathway agonist and a chemotherapeutic drug; and   administering the GSK-3 antagonist and/or Wnt canonical pathway agonist and the chemotherapeutic drug to the subject to treat the cancer.   
     
     
         2 . The method of  claim 1 , wherein the GSK-3 antagonist and/or Wnt canonical pathway agonist is 6-bromoindirubin-3′-oxime (“BIO”) or methylated BIO (“MeBIO”). 
     
     
         3 . The method of  claim 2 , wherein the GSK-3 antagonist and/or Wnt canonical pathway agonist is BIO. 
     
     
         4 . The method of  claim 2 , wherein the GSK-3 antagonist and/or Wnt canonical pathway agonist is MeBIO. 
     
     
         5 . The method of  claim 1 , wherein the chemotherapeutic drug is selected from the group consisting of temozolomide (“Tmz”), VP-16, paclitaxel, carboplatin, tumor necrosis factor-related apoptosis-inducing ligand (“TRAIL”), troglitazone (“TGZ”), pioglitazone (“PGZ”), rosiglitazone (“RGZ”), and ciglitazone (“CGZ”), procarbazine, vincristine, BCNU, CCNU, thalidomide, irinotecan, isotretinoin, imatinib, etoposide, cisplatin, daunorubicin, doxorubicin, methotrexate, mercaptopurine, fluorouracil, hydroxyurea, vinblastine, and combinations thereof. 
     
     
         6 . The method of  claim 5 , wherein the chemotherapeutic drug is Tmz. 
     
     
         7 . The method of  claim 1 , wherein the GSK-3 antagonist and/or Wnt canonical pathway agonist is 6-bromoindirubin-3′-oxime (“BIO”) or methylated BIO (“MeBIO”) and the chemotherapeutic drug is Tmz. 
     
     
         8 . The method of  claim 1 , wherein the cancer is brain cancer. 
     
     
         9 . The method of  claim 8 , wherein the brain cancer is a type of cancer selected from the group consisting of glioma, glioblastoma multiforme, astrocytoma, pituitary adenoma, acoustic neuroma, meningioma, oligodendrogliomas, gangliocytoma, ependymoma, medulloblastoma, medulloepithelioma, neuroblastoma, retinoblastoma, ependymoblastoma, pineocytoma, pineoblastoma, ependymal cell tumors, choroid plexus tumors, gliomatosis cerebri, astroblastoma and combinations thereof. 
     
     
         10 - 27 . (canceled)