Use of mtor inhibitors for prevention of intestinal polyp growth and cancer

Abstract

Disclosed are methods and compositions for the treatment or prevention of intestinal polyps or prevention of cancer in a patient who has been identified as being at risk for developing intestinal polyps or intestinal cancer. The disclosed methods and compositions include rapamycin, a rapamycin analog, or another such inhibitor of the target of rapamycin (TOR).

1 . A method for preventing intestinal polyps or intestinal cancer in a patient comprising administering an effective amount of a composition comprising rapamycin or an analog thereof to a patient who has been identified as being at risk for developing intestinal polyps or intestinal cancer. 
     
     
         2 . The method of  claim 1 , wherein the rapamycin or analog thereof is encased in a coating comprising cellulose acetate succinate, hydroxy propyl methyl cellulose phthalate co-polymer, or a polymethacrylate-based copolymer selected from the group consisting of methyl acrylate-methacrylic acid copolymer, and a methyl methacrylate-methacrylic acid copolymer. 
     
     
         3 . The method of  claim 2 , wherein the coating comprises Poly(methacylic acid-co-ethyl acrylate) in a 1:1 ratio, Poly(methacrylic acid-co-ethyl acrylate) in a 1:1 ratio, Poly(methacylic acid-co-methyl methacrylate) in a 1:1 ratio, Poly(methacylic acid-co-methyl methacrylate) in a 1:2 ratio, Poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) in a 7:3:1 ratio, Poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) in a 1:2:0.2 ratio, Poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) in a 1:2:0.1 ratio, or Poly(butyl methacylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) in a 1:2:1 ratio, a naturally-derived polymer, or a synthetic polymer, or any combination thereof. 
     
     
         4 . The method of  claim 3 , wherein the naturally-derived polymer is selected from the group consisting of alginates and their various derivatives, chitosans and their various derivatives, carrageenans and their various analogues, celluloses, gums, gelatins, pectins, gellans, polyethyleneglycols (PEGs) and polyethyleneoxides (PEOs), acrylic acid homo- and copolymers with acrylates and methacrylates, homopolymers of acrylates and methacrylates, polyvinyl alcohol PVOH), and polyvinyl pyrrolidone (PVP). 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the patient has been diagnosed with an inflammatory bowel disease. 
     
     
         7 . The method of  claim 1 , wherein the patient has been diagnosed with an intestinal polyp or an adenoma. 
     
     
         8 . The method of  claim 1 , wherein the patient has been diagnosed as having a mutation that is known to cause increased WNT signaling. 
     
     
         9 . The method of  claim 1 , wherein the patient has been diagnosed as having Familial Adenomatous Polyposis (FAP). 
     
     
         10 . The method of  claim 1 , wherein the patient has a family history of intestinal polyps or intestinal cancer. 
     
     
         11 . The method of  claim 1 , wherein the patient is between the ages of 1 to 18 years, 18 years to 50 years, or over the age of 50 years. 
     
     
         12 . The method of  claim 1 , wherein the composition comprises rapamycin or an analog thereof at a concentration of 0.001 mg to 30 mg total per dose. 
     
     
         13 . The method of  claim 1 , wherein the composition comprising rapamycin or an analog of rapamycin comprises 0.001% to 60% by weight of rapamycin or an analog of rapamycin. 
     
     
         14 . The method of  claim 1 , wherein the average blood level of rapamycin in the subject is greater than 0.5 ng per mL whole blood after administration of the composition. 
     
     
         15 . The method of  claim 1 , wherein the composition is administered orally, enterically, colonically, anally, intravenously, or dermally with a patch. 
     
     
         16 - 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the rapamycin or analog of rapamycin is administered in two or more doses; and wherein the interval of time between administration of doses comprising rapamycin or an analog of rapamycin is 1 to 3 days. 
     
     
         20 - 22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the subject is further administered a composition comprising a second active agent, wherein the second active agent is metformin, celocoxib, eflornithine, sulindac, ursodeoxycholic acid, an anti-inflammatory agent, an anti-autoimmune agent, or a cytotoxic or cytostatic anti-cancer agent. 
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 23 , wherein the composition comprising rapamycin or an analog of rapamycin is administered at the same time as the composition comprising the second active agent. 
     
     
         26 . The method of  claim 23 , wherein the composition comprising rapamycin or an analog of rapamycin is administered before or after the composition comprising the second active agent is administered; and wherein the interval of time between administration of composition comprising rapamycin or an analog of rapamycin and the composition comprising the second active agent is 1 to 30 days. 
     
     
         27 - 28 . (canceled) 
     
     
         29 . The method of  claim 1 , wherein the composition comprising rapamycin or an analog of rapamycin prevents the development of new adenomas or polyps, decreases the number or severity of the adenomatous polyps, induces a reduction in size or number of existing adenomas or polyps, prevents the conversion of adenomas or polyps into adenocarcinomas and cancer tissue, or prevents the adenomas or polyps from converting into malignant cancer that spread into other bodily tissues, organs and blood systems in a patient that has been diagnosed as having intestinal adenomas, intestinal polyps or Familial Adenomatous Polyposis (FAP). 
     
     
         30 . The method of  claim 1 , wherein the composition comprising rapamycin or an analog of rapamycin is comprised in a food or food additive.