Niclosamide for the treatment of cancer metastasis

Abstract

The invention relates to niclosamide and derivates thereof, which effectively inhibit transcription of the S100A4 gene, resulting in inhibition and/or reduction of S100A4-induced cell motility, invasiveness, metastasis and proliferation of human cancer cells.

1 .- 18 . (canceled) 
     
     
         19 . A method for treating and/or preventing cancer metastasis, comprising administering to a subject in need thereof a therapeutically effective amount of niclosamide or a niclosamide derivate. 
     
     
         20 . Method according to  claim 19 , wherein the subject is a human subject. 
     
     
         21 . Method according to  claim 19 , wherein expression of S100A4 is inhibited or reduced. 
     
     
         22 . Method according to  claim 21 , wherein the expression of S100A4 is reduced by modulating a protein complex comprising the transcription factors TCF and beta-catenin in a cancer cell. 
     
     
         23 . Method according to  claim 19 , comprising the inhibition and/or reduction of the spread of metastatic cancer. 
     
     
         24 . Method according to  claim 19 , comprising the inhibition and/or reduction of cancer cell migration and invasion. 
     
     
         25 . Method according to  claim 24 , comprising the inhibition and/or reduction of S100A4-driven cell migration and invasion. 
     
     
         26 . Method according to  claim 19 , wherein said niclosamide or niclosamide derivate is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         27 . Method according to  claim 19 , wherein the cancer is selected from the group consisting of breast cancer, colon cancer, ovarian carcinoma, osteosarcoma, cervical cancer, prostate cancer, lung cancer, synovial carcinoma, melanoma, skin and pancreatic cancer. 
     
     
         28 . Method according to  claim 19 , wherein the cancer is selected from the group consisting of an S100A4-related cancer or other cancer in which S100A4 levels are elevated, up-regulated, mutated or altered in physiology compared to non-oncogenic cells. 
     
     
         29 . Method according to  claim 19 , wherein the patient or group of patients to be treated is identified by increased expression of S100A4. 
     
     
         30 . Method according to  claim 29 , wherein a body fluid and/or a tissue of a patient to be identified is analyzed to determine S100A4 expression levels. 
     
     
         31 . Method according to  claim 19 , wherein a reduction of cancer metastasis occurs additionally by means of nucleic acid molecules. 
     
     
         32 . Method according to  claim 19 , comprising the administration of a pharmaceutical composition comprising niclosamide or a derivate thereof suitable for use as a medicament for the inhibition and/or reduction of cancer metastatsis. 
     
     
         33 . Method according to  claim 32 , comprising the administration of a pharmaceutical composition comprising at least one niclosamide or a derivate thereof with a pharmaceutically acceptable carrier, wherein said composition is a capsule, a tablet, a coated tablet, a suppository, an ointment, a cream, an injection solution and/or an infusion solution. 
     
     
         34 . Method according to  claim 32 , comprising the administration of a pharmaceutical composition, wherein the composition comprises niclosamide or derivates thereof and one or more chemotherapeutic drug. 
     
     
         35 . Method according to  claim 31 , the nucleic acids have complementarity to mRNA of components of the Wnt pathway. 
     
     
         36 . Method according to  claim 19 , comprising the administration of a pharmaceutical composition comprising niclosamide or a derivate thereof suitable for use as a medicament for the inhibition and/or reduction cancer cell migration and invasion.