Pharmaceutical composition for treatment of cancer using phenothiazine

Abstract

The present invention relates to use of antipsychotic phenothiazine derivative for treatment of cancer. The invention also provides a use for manufacture a medicament, a pharmaceutical composition and a method for treating a cancer, and/or preventing or delaying cancer recurrence based on trifluoperazine. The invention further provides a use for manufacture a medicament, a pharmaceutical composition and a method for treating cancer based on thioridazine and its enantiomers. Additionally, the invention provides a use for manufacture a medicament, a pharmaceutical composition and a method for treating KRAS mutant NSCLC comprising thioridazine.

I/We claim: 
     
         1 . Use of racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating cancer. 
     
     
         2 . The use of  claim 1 , further comprising use of one or more anti-cancer drugs in combination with the racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof in the manufacture of a combination medicament for treating cancer. 
     
     
         3 . The use of  claim 2 , wherein the anti-cancer drug is cisplatin, gefitinib, gemcitabine, pemetrexed or a combination thereof. 
     
     
         4 . The use of  claim 1 , wherein the cancer comprises non-small-cell lung carcinoma (NSCLC). 
     
     
         5 . The use of  claim 1 , wherein the cancer comprises NSCLC with KRAS mutation. 
     
     
         6 . The use of  claim 1 , wherein the cancer comprises NSCLC with KRAS wild type. 
     
     
         7 . The use of  claim 1 , wherein the medicament treats cancer by inhibiting and/or eliminating cancer stem cells (CSC). 
     
     
         8 . The use of  claim 1 , wherein the medicament treats cancer by activating AMPK in the CSCs. 
     
     
         9 . The use of  claim 1 , wherein the medicament treats cancer by inhibiting cholesterol synthesis enzymes in the CSCs. 
     
     
         10 . The use of  claim 1 , wherein (R)-thioridazine or a pharmaceutically acceptable salt thereof is used in the manufacture of a medicament of treating cancer to minimize risks of catalepsy. 
     
     
         11 . A pharmaceutical composition for treating a cancer comprising a therapeutically effective amount of racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The pharmaceutical composition of  claim 11 , further comprising an anti-cancer drug. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the anti-cancer drug is cisplatin, gefitinib, gemcitabine, pemetrexed or a combination thereof. 
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein the racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof in combination with the anti-cancer drug are in the form of one formulation or multiple formulations. 
     
     
         15 . The pharmaceutical composition of  claim 11 , wherein the effective amount of racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof treats cancer by inhibiting and/or eliminating CSCs. 
     
     
         16 . The pharmaceutical composition of  claim 11 , wherein the cancer is NSCLC. 
     
     
         17 . The pharmaceutical composition of  claim 11 , wherein the cancer is NSCLC with KRAS mutation. 
     
     
         18 . The pharmaceutical composition of  claim 11 , wherein the cancer is NSCLC with KRAS wild type. 
     
     
         19 . The pharmaceutical composition of  claim 11 , wherein the racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof treats cancer by activating AMPK in CSCs. 
     
     
         20 . The pharmaceutical composition of  claim 11 , wherein the racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof treats cancer by inhibiting cholesterol synthesis enzymes in CSCs. 
     
     
         21 . The pharmaceutical composition of  claim 11 , wherein the pharmaceutical composition comprises (R)-thioridazine or a pharmaceutically acceptable salt thereof to minimize risks of catalepsy. 
     
     
         22 . A method for treating cancer in a subject, comprising administering to the subject in need a therapeutically effective amount of a pharmaceutical composition comprising racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         23 . The method of  claim 22 , further comprising the administration of an anti-cancer drug. 
     
     
         24 . The method of  claim 23 , wherein the anti-cancer drug comprises cisplatin, gefitinib, gemcitabine, pemetrexed or a combination thereof. 
     
     
         25 . The method of  claim 22 , wherein the cancer comprises lung cancer. 
     
     
         26 . The method of  claim 22 , wherein the lung cancer comprises NSCLC. 
     
     
         27 . The method of  claim 22 , wherein the lung cancer comprises NSCLC with KRAS mutation. 
     
     
         28 . The method of  claim 22 , wherein the lung cancer comprises NSCLC with KRAS wild type. 
     
     
         29 . The method of  claim 22 , wherein the lung cancer is resistant to gefitinib, erlotinib, cetuximab, matuzumab, or panitumumab. 
     
     
         30 . The method of  claim 22 , wherein (R)-thioridazine or a pharmaceutically acceptable salt thereof is administered to the subject in need to minimize risks of catalepsy. 
     
     
         31 . A method for selecting clinical trial subjects for racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof for treating NSCLC comprising the step of selecting clinical trial subjects who are afflicted with NSCLC with KRAS mutation. 
     
     
         32 . A pharmaceutical composition comprising racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof for elimination of cancer cells with KRAS mutation. 
     
     
         33 . A pharmaceutical composition comprising racemic thioridazine, (S)-thioridazine, (R)-thioridazine or a pharmaceutically acceptable salt thereof for activating AMPK in cells.