Pyrvinium pamoate therapies and methods of use

Abstract

The disclosure relates to a method of treating cancer by administering to the subject a therapeutically effective amount of a composition comprising pyrvinium pamoate, optionally in combination with at least one additional therapeutic agent or modality.

1 - 129 . (canceled) 
     
     
         130 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject a synergistic combination of a composition comprising pyrvinium pamoate, and a composition comprising at least one other chemotherapeutic agent. 
     
     
         131 . The method according to  claim 130 , wherein the composition comprising pyrvinium pamoate further comprises a nanoparticle. 
     
     
         132 . The method according to  claim 131 , wherein the nanoparticle comprises a liposome, a micelle, a polymer-based nanoparticle, a lipid-polymer based nanoparticle, a metal based nanoparticle, a nanocrystal, a carbon nanotube based nanoparticle or a polymeric micelle. 
     
     
         133 . The method according to  claim 132 , wherein the polymer-based nanoparticle comprises a multiblock copolymer, a diblock copolymer, a polymeric micelle or a hyperbranched macromolecule. 
     
     
         134 . The method according to  claim 132 , wherein the polymer-based nanoparticle comprises a poly(lactic-co-glycolic acid) PLGA polymer. 
     
     
         135 . The method according to  claim 131 , wherein the nanoparticle further comprises a targeting agent. 
     
     
         136 . The method according to  claim 135 , wherein the targeting agent comprises a peptide ligand, a nucleotide ligand, a polysaccharide ligand, a fatty acid ligand, a lipid ligand, a small molecule ligand, an antibody, an antibody fragment, an antibody mimetic or an antibody mimetic fragment. 
     
     
         137 . The method according to  claim 135 , wherein the targeting agent comprises hyaluronic acid. 
     
     
         138 . The method according to  claim 130 , wherein the cancer comprises a colon cancer, a breast cancer, a liver cancer, a lung cancer, a brain cancer, a pancreatic cancer or a renal cancer. 
     
     
         139 . The method according to  claim 130 , wherein the cancer is a rare cancer. 
     
     
         140 . The method according to  claim 139 , wherein the rare cancer is a blastoma, a glioma, a sarcoma, a carcinoma, a neuroendocrine cancer, a mesothelioma, a chordoma, a thymic cancer, a gastrointestinal stromal tumor or a pheochromocytoma. 
     
     
         141 . The method according to  claim 140 , wherein:
 (a) the blastoma comprises a neuroblastoma;   (b) the sarcoma comprises an Ewing's sarcoma, a leiomyosarcoma, an angiosarcoma or a rhabdomyosarcoma;   (c) the carcinoma comprises an adenoid cystic carcinoma (ACC), a uterine serous carcinoma, a cholangiocarcinoma, a colorectal carcinoma, an esophageal carcinoma, a hepatocellular carcinoma, a pancreatic carcinoma, a small cell lung carcinoma, an adrenocortical carcinoma, an ovarian carcinoma, a gastric carcinoma or a thymic carcinoma;   (d) the neuroendocrine cancer comprises an adrenocortical carcinoma, a carcinoid tumor or a thymic cancer; or   (e) the thymic cancer comprises a thymoma or a thymic carcinoma.   
     
     
         142 . The method according to  claim 141 , wherein the ovarian carcinoma comprises an endometrioid or epithelial ovarian carcinoma. 
     
     
         143 . The method according to  claim 130 , wherein:
 (a) the synergy is measured using the Chou-Talalay method in at least one cancer cell line; or   (b) the synergy comprises a CI of less than 0.9 when measured at at least three concentrations of the composition comprising pyrvinium pamoate and the at least one other chemotherapeutic agent in at least one cancer cell line.   
     
     
         144 . The method according to  claim 130 , wherein the at least one other chemotherapeutic agent comprises a taxane, a Vinca alkaloid, a platinum based antineoplastic drug, a Topoisomerase inhibitor, a thymidylate synthase inhibitor, a DNA intercalating agent, a DNA alkylating agent, cyclin dependent kinase (CDK) inhibitor, a mechanistic target of rapamycin kinase (mTOR) inhibitor, a DNA damaging agent, receptor tyrosine kinase (RTK) inhibitor or a combination chemotherapy. 
     
     
         145 . The method according to  claim 144 , wherein:
 (a) the taxane comprises Paclitaxel or Docetaxel;   (b) the Vinca alkaloid comprises Vinblastine, Vincristine or Vinorelbine;   (c) the platinum based antineoplastic drug comprises Cisplatin, Carboplatin or Oxaliplatin;   (d) the topoisomerase inhibitor comprises Irinotecan or Etoposide;   (e) the thymidylate synthase inhibitor comprises 5-Fluorouracil (5-FU);   (f) the DNA intercalating agent comprises Doxorubicin;   (g) the DNA alkylating agent comprises Dacarbazine, Temozolomide, Cyclophosphamide or Ifosfamide;   (h) the CDK inhibitor comprises an inhibitor of CDK4, an inhibitor of CDK6 or an inhibitor of CDK4 and CDK6;   (i) the mTOR inhibitor comprises Rapamycin, Temsirolimus, Everolimus or Ridaforolimus   (j) the DNA damaging agent comprises Gemcitabine; or   (k) the RTK inhibitor comprises erlotinib, imatinib or sorafenib.   
     
     
         146 . The method according to  claim 145 , wherein the CDK inhibitor comprises Abemaciclib, Palbociclib or Ribociclib. 
     
     
         147 . The method according to  claim 130 , wherein the composition comprising pyrvinium pamoate and the at least one other chemotherapeutic agent are in the same composition. 
     
     
         148 . The method according to  claim 147 , wherein the composition comprising pyrvinium pamoate and the at least one other chemotherapeutic agent are formulated in a nanoparticle. 
     
     
         149 . The method according to  claim 130 , wherein the composition comprising pyrvinium pamoate and the least one other chemotherapeutic agent are administered simultaneously, are administered sequentially, are administered in alternating series or are administered in temporal proximity. 
     
     
         150 . The method according to  claim 130 , wherein the composition comprising pyrvinium pamoate is administered orally or parenterally, and wherein the at least one other chemotherapeutic agent is administered orally or parenterally. 
     
     
         151 . The method according to  claim 130 , wherein the method of treatment further comprises at least one additional cancer treatment. 
     
     
         152 . The method according to  claim 151 , wherein the at least one additional cancer treatment comprises a surgical procedure to remove at least one tumor of the cancer, at least one dose of a radiation therapy, at least one additional chemotherapeutic agent, a therapeutic antibody, at least one immune checkpoint modulator, or a combination thereof. 
     
     
         153 . The method according to  claim 151 , wherein the composition comprising pyrvinium pamoate is suitable for administration at the same time as the at least one dose of radiation therapy, prior to the at least one dose of radiation therapy, after the at least one dose of radiation therapy or in temporal proximity to the at least one dose of radiation therapy. 
     
     
         154 . The method according to  claim 130 , wherein the method of treatment alleviates a sign or a symptom of the cancer.