Novel compositions and methods for cancer treatment

Abstract

The present invention relates to the composition and methods of use of Stat3 pathway inhibitors or cancer stem cell inhibitors in combination treatment of cancer.

1 .- 111 . (canceled) 
     
     
         112 . A method for treating a non-cancer disorder in a subject in need thereof, comprising administering:
 a) a composition comprising a therapeutically effective amount of at least one first agent chosen from 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-dione, 2-acetyl-7-chloronaphtho[2,3-b]furan-4,9-dione, 2-acetyl-7-fluoro-naphtho[2,3-b]furan-4,9-dione, 2-acetylnaphtho[2,3-b]furan-4,9-dione, 2-ethyl-naphtho[2,3-b]furan-4,9-dione, and pharmaceutically acceptable salts thereof; and   b) a composition comprising a therapeutically effective amount of at least one second agent.   
     
     
         113 . The method according to  claim 112 , wherein the non-cancer disorder is chosen from autoimmune diseases, inflammatory diseases, inflammatory bowel diseases, arthritis, asthma, systemic lupus erythematosus, autoimmune demyelination disorders, Alzheimer's disease, stroke, ischemia reperfusion injuries, and multiple sclerosis. 
     
     
         114 . The method according to  claim 112 , wherein the at least one second agent is chosen from cytotoxic agents, targeted agents, radiotherapy agents, biologic agents, hormonal agents, HDAC inhibitors, retinoid agents, checkpoint activators, proteasome inhibitors, adjuvant agents, and adjunctive agents. 
     
     
         115 . The method according to  claim 112 , wherein the non-cancer disorder is refractory to chemotherapy or radiotherapy. 
     
     
         116 . A method for treating a cancer disorder in a subject in need thereof, comprising administering:
 a) a composition comprising a therapeutically effective amount of at least one first agent chosen from 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-dione, 2-acetyl-7-chloronaphtho[2,3-b]furan-4,9-dione, 2-acetyl-7-fluoro-naphtho[2,3-b]furan-4,9-dione, 2-acetylnaphtho[2,3-b]furan-4,9-dione, 2-ethyl-naphtho[2,3-b]furan-4,9-dione, and pharmaceutically acceptable salts thereof; and   b) a composition comprising a therapeutically effective amount of at least one second agent chosen from growth factor-targeting agents, kinase-targeting agents, angiogenesis inhibitors, DNA-damaging agents, antimitotic agents, and antimetabolite agents,   wherein the cancer disorder is selected from head and neck cancer, brain cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, ovarian cancer, cervical cancer, uterine cancer, gastrointestinal cancer, kidney cancer, bladder cancer, vulvar cancer, cancer of the peritoneum, prostate cancer, thyroid cancer, sarcomas, squamous cell cancer, melanoma, leukemia, lymphoma, and myeloma, and   wherein said cancer expresses activated Stat3.   
     
     
         117 . The method according to  claim 116 , wherein the cancer disorder is refractory to chemotherapy or radiotherapy. 
     
     
         118 . A pharmaceutical composition comprising:
 a) a therapeutically effective amount of at least one first agent chosen from 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-dione, 2-acetyl-7-chloronaphtho[2,3-b]furan-4,9-dione, 2-acetyl-7-fluoro-naphtho[2,3-b]furan-4,9-dione, 2-acetylnaphtho[2,3-b]furan-4,9-dione, 2-ethyl-naphtho[2,3-b]furan-4,9-dione, and pharmaceutically acceptable salts thereof; and   b) a therapeutically effective amount of at least one second agent chosen from cytotoxic agents, targeted agents, radiotherapy agents, biologic agents, hormonal agents, HDAC inhibitors, retinoid agents, checkpoint activators, proteasome inhibitors, adjuvant agents, adjunctive agents, and pharmaceutically acceptable salts thereof.