Par-4 agonists for the treatment of cancer

Abstract

Disclosed herein are methods of treating cancers by administration of a PAR-4 agonist.

1 - 15 . (canceled) 
     
     
         16 . A method for treating cancer, comprising increasing expression of prostate apoptosis response 4 (PAR-4) in a patient having cancer by administering one or more agents consisting of cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, as a single agent or in combination with an anti-cancer agent selected from the group consisting of kinase inhibitors, microtubule inhibitors, topoisomerase inhibitors, alkylating agents, antitumor antibiotics, antimetabolites, proteosome inhibitors, PARP inhibitors, HDAC inhibitors, Hedgehog signaling pathway inhibitors, hormonal agents, mTOR inhibitors, salts thereof, and combinations thereof. 
     
     
         17 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with a kinase inhibitor selected from afatinib, alectinib, axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, crizotinib, dabrafenib dasatinib, erlotinib, gefitinib, ibrutinib, idelalisib, imatinib, lapatinib, lenvatinib, nilotinib, osimertinib, palbociclib, ponatinib, pazopanib, regorafenib, ruxolitinib, sorafenib, sunitinib, trametinib, vandetanib, vemurafenib, pharmaceutically acceptable salts thereof, and combinations thereof. 
     
     
         18 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with a microtubule inhibitor selected from cabazitaxel, docetaxel, eribulin, ixabepilone, omacetaxine paclitaxel, vinblastine, vincristine, vinorelbine, salts thereof, and combinations thereof. 
     
     
         19 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with an alkylating agent selected from bendamustine, busulfan, carboplatin, carmustine, cisplatin, chlorambucil, cyclophosphamide, dacarbazine, ifosfamide, lomustine, melphalan, mechlorethamine, procarbazine, temozolomide, thiotepa, trabectedin, salts thereof, and combinations thereof. 
     
     
         20 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with an antimetabolite selected from azacitidine, capecitabine, cladribine, clofarabine cytarabine, decitabine, fludarabine, fluorouracil, gemcitabine, hydroxyurea, mercaptopurine, methotrexate, nelarabine, pemetrexed, pralatrexate, thioguanine, trifluridine, salts thereof, and combinations thereof. 
     
     
         21 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with a topoisomerase inhibitor selected from irinotecan, topotecan, etoposide, salts thereof, and combinations thereof. 
     
     
         22 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with an antitumor antibiotic selected from adriamycin, bleomycin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, mitomycin C, mitoxantrone, rubidomycin, salts thereof, and combinations thereof. 
     
     
         23 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with a proteasome inhibitor selected from bortezomib, carfilzomib, ixazomib, salts thereof, and combinations thereof. 
     
     
         24 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with a PARP inhibitor selected from the group consisting of olaparib, an HDAC inhibitor selected from vorinostat, belinostat, romidepsin, panobinostat, a Hedgehog signaling pathway inhibitor selected from vismodegib, sonidegib, salts thereof, and combinations thereof. 
     
     
         25 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with a hormonal agent selected from the group consisting of abiraterone, anastrozole, bicalutamide, degarelix, enzalutamide, exemestane, flutamide, fulvestrant, goserelin, letrozole leuprolide, megestrol, raloxifene tamoxifen, toremifene, salts thereof, and combinations thereof. 
     
     
         26 . The method according to  claim 16 , wherein the cefuroxime, a pharmaceutically acceptable salt or prodrug thereof, is administered in combination with an mTOR inhibitor selected from the group consisting of everolimus, temsirolimus, salts thereof, and combinations thereof. 
     
     
         27 . The method according to  claim 16 , wherein the cefuroxime prodrug comprises cefuroxime axetil. 
     
     
         28 . The method according to  claim 16 , further comprising administering ionizing radiation to the patient, performing a surgical intervention on the patient, or a combination thereof. 
     
     
         29 . The method according to  claim 29 , wherein the cefuroxime is administered for a period of at least one week prior to commencing radiation treatment or surgical intervention. 
     
     
         30 . The method according to  claim 16 , wherein the cefuroxime and additional chemotherapeutic acid are administered in an intermittent dosing regimen. 
     
     
         31 . The method according to  claim 16 , wherein the cefuroxime and additional chemotherapeutic acid are administered simultaneously. 
     
     
         32 . The method according to  claim 16 , wherein the cefuroxime and additional chemotherapeutic acid are administered separately. 
     
     
         33 . A pharmaceutical composition comprising cefuroxime and at least one additional therapeutic agent selected from the group consisting of monoclonal antibodies, kinase inhibitors, microtubule inhibitors, topoisomerase inhibitors, alkylating agents, antitumor antibiotics, antimetabolites, proteosome inhibitors, PARP inhibitors, HDAC inhibitors, Hedgehog signaling pathway inhibitors, hormonal agents, mTOR inhibitors, salts thereof, and combinations thereof. 
     
     
         34 . A kit comprising cefuroxime and at least one other therapeutic agent selected from the group consisting of monoclonal antibodies, kinase inhibitors, microtubule inhibitors, topoisomerase inhibitors, alkylating agents, antitumor antibiotics, antimetabolites, proteosome inhibitors, PARP inhibitors, HDAC inhibitors, Hedgehog signaling pathway inhibitors, hormonal agents, mTOR inhibitors, salts thereof, and combinations thereof.