Methods for malignant tumors with rnai molecules targeted to hsp47

Abstract

This invention provides methods for preventing, treating or ameliorating one or more symptoms of a malignant tumor in a mammal in need thereof, by administering to the mammal a therapeutically effective amount of a composition comprising RNAi molecules, where the RNAi molecules can be active in reducing expression of Hsp47.

What is claimed is: 
     
         1 . A method for preventing, treating or ameliorating one or more symptoms of a malignant tumor in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a composition comprising RNAi molecules active in reducing expression of Hsp47. 
     
     
         2 . The method of  claim 1 , wherein the mammal is a human, and the Hsp47 is a human Hsp47. 
     
     
         3 . The method of  claim 1 , wherein the malignant tumor overexpresses Hsp47. 
     
     
         4 . The method of  claim 1 , wherein the RNAi molecules decrease expression of Hsp47 in the mammal. 
     
     
         5 . The method of  claim 1 , wherein the composition retains at least 80% of the activity of the RNAi molecules after 1 hour exposure to human serum. 
     
     
         6 . The method of  claim 1 , wherein the RNAi molecules are siRNAs or shRNAs. 
     
     
         7 . The method of  claim 1 , wherein each RNAi molecule comprises a duplex region, wherein the duplex region comprises a nucleotide sequence corresponding to a target sequence of Hsp47 mRNA. 
     
     
         8 . The method of  claim 1 , wherein the administration decreases expression of Hsp47 in the mammal by at least 5% for at least 5 days. 
     
     
         9 . The method of  claim 1 , wherein the administration decreases the volume of the malignant tumor in the mammal by at least 5%. 
     
     
         10 . The method of  claim 1 , wherein the method reduces one or more symptoms of the malignant tumor, or delays or terminates the progression of the malignant tumor. 
     
     
         11 . The method of  claim 1 , wherein the administration reduces growth of malignant tumor cells in the subject. 
     
     
         12 . The method of  claim 1 , wherein the administration reduces growth for at least 2% of the malignant tumor cells in the subject. 
     
     
         13 . The method of  claim 1 , wherein the tumor cells overexpress wild-type Hsp47 RNA or protein. 
     
     
         14 . The method of  claim 1 , wherein the tumor is a sarcoma selected from the group consisting of lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. 
     
     
         15 . The method of  claim 1 , wherein the malignant tumor is a sarcoma selected from the group of lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas, colorectal carcinoma, breast cancer, and fibrosarcoma. 
     
     
         16 . The method of  claim 1 , wherein the malignant tumor is located in an anatomical region selected from the group of lung, liver, pancreas, colon, kidney, heart, bone, skin, intestine and joints, and any combination thereof. 
     
     
         17 . The method of  claim 1 , wherein the administration is performed from 1 to 12 times per day. 
     
     
         18 . The method of  claim 1 , wherein the administration is performed for a duration of 1, 2, 3, 4, 5, 6 or 7 days. 
     
     
         19 . The method of  claim 1 , wherein the administration is performed for a duration of 1, 2, 3, 4, 5, 6, 8, 10 or 12 weeks. 
     
     
         20 . The method of  claim 1 , wherein the administration is a dose of from 0.01 to 2 mg/kg of the RNAi molecules at least once per day for a period up to twelve weeks. 
     
     
         21 . The method of  claim 1 , wherein the administration provides a mean AUC(0-last) of from 1 to 1000 ug*min/mL and a mean C max  of from 0.1 to 50 ug/mL for the Hsp47 RNAi molecule. 
     
     
         22 . The method of  claim 1 , wherein the administration is intravenous injection, intradermal injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, oral, topical, infusion, or inhaled.