Combination therapy for the treatment of cancer

Abstract

Described are methods and compositions for treating cancer that include a dopamine receptor (DR) antagonist such as thioridazine and a chemotherapeutic agent. Optionally, the chemotherapeutic agent is a DNA synthesis inhibitor such as cytarabine or a microtubule inhibitor such as paclitaxel or docetaxel. The methods and compositions are useful for the treatment of cancers such as acute myeloid leukemia.

1 .- 20 . (canceled) 
     
     
         21 . A method of treating cancer or a pre-cancerous disorder in a subject in need thereof comprising administering to the subject a dopamine receptor antagonist and a chemotherapeutic agent. 
     
     
         22 . The method of  claim 21 , wherein the chemotherapeutic agent is a DNA synthesis inhibitor or a microtubule inhibitor. 
     
     
         23 . The method of  claim 22 , wherein the DNA synthesis inhibitor is a DNA elongation terminator. 
     
     
         24 . The method of  claim 23 , wherein the DNA elongation terminator is a deoxycytidine analogue. 
     
     
         25 . The method of  claim 24 , wherein the deoxycytidine analogue is gemcitabine, decitabine, vidaza, troxacitabine, thiarabine or sapacitabine. 
     
     
         26 . The method of  claim 23 , wherein the DNA elongation terminator is cytarabine, fludarabine, nelarabine, cladribine, or clofarabine. 
     
     
         27 . The method of  claim 23 , wherein the DNA elongation terminator is cytarabine. 
     
     
         28 . The method of  claim 21 , wherein the dopamine receptor antagonist is a D2 family dopamine receptor antagonist. 
     
     
         29 . The method of  claim 21 , wherein the dopamine receptor antagonist is selected from Table 1. 
     
     
         30 . The method of  claim 21 , wherein the dopamine receptor antagonist is a phenothiazine derivative. 
     
     
         31 . The method of  claim 30 , wherein the phenothiazine derivative is thioridazine, chlorpromazine, levomepromazine, mesoridazine, fluphenazine, perphenazine, prochlorperazine, or trifluoperazine. 
     
     
         32 . The method of  claim 30 , wherein the phenothiazine derivative is thioridazine. 
     
     
         33 . The method of  claim 21 , wherein the cancer or pre-cancerous disorder is leukemia or a lymphoma. 
     
     
         34 . The method of  claim 33 , wherein the leukemia is acute myeloid leukemia (AML). 
     
     
         35 . The method of  claim 21 , wherein the subject is in remission. 
     
     
         36 . The method of  claim 21 , wherein the subject is a human. 
     
     
         37 . The method of  claim 21 , wherein the dopamine receptor antagonist and a chemotherapeutic agent and conjugated through a linker. 
     
     
         38 . A composition comprising a dopamine receptor antagonist and a chemotherapeutic agent. 
     
     
         39 . A conjugate comprising a dopamine receptor antagonist and a chemotherapeutic agent. 
     
     
         40 . The conjugate of  claim 39 , wherein the dopamine receptor antagonist and the chemotherapeutic agent are conjugated through a linker.