Methods of Inhibiting Tumorigenesis in Colon Adenocarcinoma and Compositions Therefor

Abstract

Described herein are methods and compositions for the treatment of colon cancers.

What is claimed is: 
     
         1 . A method of inhibiting tumorigenesis in a subject who has, or is suspected of having, a colon cancer-related disease in which at least one miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof, is down-regulated or up-regulated in the cancer cells of the subject, relative to control cells, comprising:
 (1) when the at least one miR gene product is down-regulated in the cancer cells, administering to the subject an effective amount of at least one isolated miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof, such that tumorigenesis is inhibited in the subject; or   (2) when the at least one miR gene product is up-regulated in the cancer cells, administering to the subject an effective amount of at least one compound for inhibiting expression of the at least one miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof, such that tumorigenesis is inhibited in the subject.   
     
     
         2 . The method of  claim 1 , wherein the at least one isolated miR gene product in step (1) and/or in step (2) is miR-21 or an isolated variant or biologically-active fragment or functional equivalent thereof, or an antibody that binds thereto. 
     
     
         3 . A method of inhibiting tumorigenesis in a subject who has a colon cancer, comprising:
 (1) determining the amount of at least one miR gene product in cancer cells from the subject, relative to control cells; and   (2) altering the amount of miR gene product expressed in the cancer cells by:
 (i) administering to the subject an effective amount of at least one isolated miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof, if the amount of the miR gene product expressed in the cancer cells is less than the amount of the miR gene product expressed in control cells; or 
 (ii) administering to the subject an effective amount of at least one compound for inhibiting expression of the at least one miR gene product, if the amount of the miR gene product expressed in the cancer cells is greater than the amount of the miR gene product expressed in control cells, 
   such that tumorigenesis is inhibited in the subject.   
     
     
         4 . The method of  claim 3 , wherein the at least one isolated miR gene product in step (i) is miR-21 or an isolated variant or biologically-active fragment thereof. 
     
     
         5 . The method of  claim 3 , wherein the at least one miR gene product in step (ii) is selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof, or an isolated variant or biologically-active fragment thereof. 
     
     
         6 . A pharmaceutical composition for treating a colon cancer-related disease, comprising:
 at least one miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof; and,   a pharmaceutically-acceptable carrier.   
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the at least one miR gene product corresponds to a miR gene product that is up- or down-regulated in cancer cells relative to suitable control cells. 
     
     
         8 . The pharmaceutical composition of  claim 6 , wherein the miR gene product is miR-21. 
     
     
         9 . The pharmaceutical composition of  claim 6 , wherein the colon cancer-related disease is adenocarcinoma. 
     
     
         10 . A pharmaceutical composition for treating a colon cancer, comprising
 at least one miR expression-inhibition compound, and   a pharmaceutically-acceptable carrier,   wherein the at least one miR expression-inhibition compound is specific for a miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof.   
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the at least one miR expression-inhibition compound is specific for a miR gene product that is up- or down-regulated in cancer cells relative to suitable control cells. 
     
     
         12 . A method for treating, preventing, reversing or limiting the severity of a colon cancer-related disease complication in an individual in need thereof, comprising:
 administering to the individual an agent that interferes with at least one colon cancer-related disease response signaling pathway, in an amount sufficient to interfere with such signaling,   wherein the agent comprises at least one miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof.   
     
     
         13 . The method of  claim 12 , wherein the at least one miR gene product is miR-21. 
     
     
         14 . An agent that interferes with at least one colon cancer-related disease response signaling pathway, for the manufacture of a medicament for treating, preventing, reversing or limiting the severity of a colon cancer-related disease complication in an individual,
 wherein the agent comprises at least one miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof.   
     
     
         15 . The agent of  claim 14 , wherein the at least one miR gene product is miR-21. 
     
     
         16 . A method of treating, preventing, reversing or limiting the severity of a colon cancer-related disease complication in an individual in need thereof, comprising
 administering to the individual an agent that interferes with at least one colon cancer-related disease response cascade,   wherein the agent comprises at least one miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof.   
     
     
         17 . The method of  claim 16 , wherein the at least one miR gene product is miR-21. 
     
     
         18 . An agent that interferes with at least one colon cancer-related disease response cascade, for the manufacture of a medicament for treating, preventing, reversing or limiting the severity of a colon cancer-related disease complication in an individual,
 wherein the agent comprises at least one miR gene product selected from the group consisting of miR-20a, miR-21, miR-106a, miR-181b, miR-203 and combinations thereof.   
     
     
         19 . The agent of  claim 18 , wherein the at least one miR gene product is miR-21.