Treatment of Cancer with Naltrexone

Abstract

The present invention provides novel therapeutic applications of low dose naltrexone (LDN). Said applications have been determined in light of the discovery by the present inventors that naltrexone acts as an antagonist of Toll-like receptor 9 (TLR9), an innate immune receptor which elicits the production of inflammatory cytokines when agonised. Chronic inflammation and TLR9 overexpression are characteristics of a number of disorders, including certain cancers. Accordingly, the present invention provides novel uses of naltrexone in the treatment of a subject having a disorder characterised by TLR9 overexpression and/or overactivity of TLR9-mediated signalling. The present invention also provides novel uses of naltrexone in the supportive care of subject having a tumour/cancer, and methods of treating and providing supportive care to a subject, comprising the administration of naltrexone.

1 . A method of treating a subject having a tumour/cancer, wherein the method comprises:
 testing the tumour/cancer in the subject for TLR9 expression and/or activity of TLR9-mediated signalling; and   administering to the subject a pharmaceutical composition comprising naltrexone,   wherein the subject is or has been administered at least one chemotherapeutic agent.   
     
     
         2 . The method according to  claim 1 , wherein the tumour/cancer is selected from the group consisting of breast cancer, cervical squamous cell carcinoma, gastric carcinoma, glioma, hepatocellular carcinoma, lung cancer, melanoma, prostate cancer, recurrent glioblastoma, recurrent non-Hodgkin lymphoma, and colorectal cancer. 
     
     
         3 . The method according to  claim 1 , wherein the at least one chemotherapeutic agent is selected from the group consisting of Revlimid, cyclophosphamide, Gemcitabine and carboplatin. 
     
     
         4 . The method according to  claim 3 , wherein the Revlimid is administered at a dose between 5 mg and 25 mg, the cyclophosphamide is administered at a dose between 50 mg and 100 mg, and/or the Gemcitabine is administered at a dose between 250 mg and 2000 mg. 
     
     
         5 . The method according to  claim 1 , wherein macrophages; B cells; and/or dendritic cells of the subject are characterised as having the TLR9 expression. 
     
     
         6 . The method according to  claim 1 , wherein plasmacytoid dendritic cells of the subject are characterised as having the TLR9 expression. 
     
     
         7 . The method according to  claim 1 , wherein the subject is or has been administered at least one other immunomodulator. 
     
     
         8 . The method according to  claim 1 , wherein the subject is or has been administered at least one immune agonist. 
     
     
         9 . The method according to  claim 8 , wherein the at least one immune agonist is selected from the group consisting of cyclophosphamide, Revlimid, Imiquimod, a whole cell Mycobacteria, Daunorubicin, Oxaliplatin, 5-Fluorouracil, Gemcitabine, and Zometa. 
     
     
         10 . The method according to  claim 9 , wherein the whole cell Mycobacteria is a rough strain of Mycobacteria  obuense  or Mycobacteria  vaccae.    
     
     
         11 . The method according to  claim 1 , wherein the naltrexone, as part of the pharmaceutical composition, is administered to the subject at a dose between 0.01 mg/kg and 0.08 mg/kg. 
     
     
         12 . The method according to  claim 1 , wherein the naltrexone, as part of the pharmaceutical composition, is administered to the subject at a dose between, 0.03 mg/kg and 0.06 mg/kg. 
     
     
         13 . The method according to  claim 1 , wherein the naltrexone, as part of the composition, is administered to the subject at a dose between 0.04 mg/kg and 0.05 mg/kg.