Compositions and Methods for Treating Epithelial Cancer

Abstract

The present invention provides the eutomeric isomer of the compound of formula (I), or a salt or solvate thereof, which can be used to treat epithelial cancer in a subject. In certain embodiments, the compound of formula (I) can be used in combination with AICAR and/or cisplatin.

1 - 21 . (canceled) 
     
     
         22 . A method of treating epithelial cancer in a subject suffering from the cancer, wherein the epithelial cancer is at least one cancer selected from the group consisting of endometrial, pancreatic, and renal, the method comprising administering to the subject in need thereof a therapeutically effective amount of the eutomeric isomer of the compound of formula (I), which is 3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol, or a salt or solvate thereof: 
       
         
           
           
               
               
           
         
       
     
     
         23 . The method of  claim 22 , wherein the compound is at least one selected from the group consisting of: (3S,4R)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol; (3R,4S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol; (3S,4S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol; and (3R,4R)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol. 
     
     
         24 . The method of  claim 22 , further comprising administering to the subject a therapeutically effective amount of at least one agent selected from the group consisting of an AMPK activator, chemotherapeutic drug, or any salt, solvate, enantiomer, diastereoisomer or tautomer thereof. 
     
     
         25 . The method of  claim 24 , wherein the amount of the compound and the amount of the at least one agent administered to the subject are such that at least one of the following applies: (a) administration of the amount of the compound is not therapeutically effective in treating the epithelial cancer in the absence of co-administration of the amount of the at least one agent; and (b) administration of the amount of the at least one agent is not therapeutically effective in treating the epithelial cancer in the absence of co-administration of the amount of the compound. 
     
     
         26 . The method of  claim 24 , wherein the subject experiences an improved disease outcome when administered the compound and the at least one agent, as compared to the disease outcome when the subject is administered the compound in the absence of the at least one agent or when the subject is administered the at least one agent in the absence of the compound, wherein the disease outcome is at least one selected from the group consisting of survival rate increase, tumor size reduction, and metastatic proliferation reduction. 
     
     
         27 . The method of  claim 24 , wherein the chemotherapeutic drug is at least one selected from the group consisting of Paclitaxel, Cisplatin, Carboplatin, Topotican and Doxoribicin. 
     
     
         28 . The method of  claim 24 , wherein the AMPK activator is at least one selected from the group consisting of 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), metformin and 5-[3-[4-[2-(4-fluorophenyl)ethoxy] phenyl]propyl]-2-furancarboxylic acid. 
     
     
         29 . The method of  claim 24 , wherein the at least one agent is coformulated with the compound. 
     
     
         30 . The method of  claim 22 , wherein the subject is administered the compound as part of a maintenance treatment after having been treated with at least one chemotherapy. 
     
     
         31 . The method of  claim 30 , wherein the subject has suffered at least one epithelial cancer recurrence. 
     
     
         32 . The method of  claim 22 , wherein the compound is administered to the subject (i) once per day, and every week day; or (ii) once per day, and five days out of every seven week days, with two consecutive rest days wherein the compound is not administered to the subject. 
     
     
         33 . The method of  claim 30 , wherein the maintenance treatment prevents or delays in the subject at least one selected from the group consisting of epithelial cancer recurrence and epithelial cancer metastasis. 
     
     
         34 . The method of  claim 22 , wherein the compound is formulated in a pharmaceutical composition as part of a nanoparticle, which is optionally coated with a peptide comprising ArgGlyAsp. 
     
     
         35 . The method of  claim 22 , wherein the epithelial cancer is at least one selected from the group consisting of recurring and resistant to at least one chemotherapy. 
     
     
         36 . A pharmaceutical composition comprising
 an amount of the eutomeric isomer of the compound of formula (I), which is 3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methylchroman-7-ol, or a salt or solvate thereof, and   an amount of at least one AMPK activator, or a salt or solvate thereof,   wherein administration of the composition to a subject suffering from epithelial cancer treats or prevents the cancer.   
     
     
         37 . The pharmaceutical composition of  claim 36 , wherein the subject is female and suffering from ovarian cancer. 
     
     
         38 . The pharmaceutical composition of  claim 36 , wherein the amount of the compound and the amount of the at least one AMPK activator in the composition are such that at least one of the following applies:
 (a) administration of the amount of the compound in the composition is not therapeutically effective in treating the epithelial cancer in the absence of the co-administration of the amount of at least one AMPK activator in the composition; and   (b) administration of the amount of the at least one AMPK activator in the composition is not therapeutically effective in treating the epithelial cancer in the absence of co-administration of the amount of the compound in the composition.   
     
     
         39 . The pharmaceutical composition of claim  1 , wherein the subject experiences an improved disease outcome when administered the pharmaceutical composition, as compared to the disease outcome when the subject is administered the amount of the compound in the absence of the amount of the at least one AMPK activator or when the subject is administered the amount of the at least one AMPK activator in the absence of the amount of the compound, wherein the disease outcome is at least one selected from the group consisting of survival rate increase, tumor size reduction, and metastatic proliferation reduction.