Use of Cysteamine and Derivatives Thereof to Suppress Tumor Metastases

Abstract

The present disclosure is directed to methods for inhibiting or suppressing metastasis of a tumor in a mammalian subject using a cysteamine product, e.g., cysteamine or cystamine or derivatives thereof. Also described herein is a method for treating pancreatic cancer in a mammalian subject by administering a cysteamine product described herein.

1 . A method of inhibiting or suppressing metastasis of a tumor in a mammalian subject comprising administering cysteamine, cystamine or pharmaceutically acceptable salts thereof to the subject in an amount effective to inhibit metastasis of the tumor. 
     
     
         2 . A method of treating pancreatic cancer in a mammalian subject comprising administering cysteamine, cystamine or pharmaceutically acceptable salts thereof to the subject in an amount effective to treat the cancer. 
     
     
         3 . The method of  claim 1  or  claim 2 , wherein the cysteamine, cystamine or pharmaceutically acceptable salts thereof is administered orally. 
     
     
         4 . The method of any one of the preceding claims, wherein the cysteamine, cystamine or pharmaceutically acceptable salts thereof is formulated for delayed release. 
     
     
         5 . The method of  claim 4 , wherein the delayed release formulation comprises an enteric coating that releases the cysteamine or cystamine when the formulation reaches the small intestine or a region of the gastrointestinal tract of a subject in which the pH is greater than about pH 4.5. 
     
     
         6 . The method of any one of the preceding claims, wherein the cysteamine, cystamine or pharmaceutically acceptable salts thereof is administered less than four times a day. 
     
     
         7 . The method of any one of the preceding claims, wherein the cysteamine, cystamine or pharmaceutically acceptable salts thereof is administered twice a day. 
     
     
         8 . The method of any one of the preceding claims, wherein the administering results in increased thiol levels compared to levels before administration of the cysteamine, cystamine or pharmaceutically acceptable salts thereof. 
     
     
         9 . The method of any one of the preceding claims, wherein the cysteamine, cystamine or pharmaceutically acceptable salts thereof is formulated in a tablet or capsule which is enterically coated. 
     
     
         10 . The method of any one of  claims 1  and  3 - 9 , wherein the tumor is associated with a cancer selected from the group consisting of breast cancer, melanoma, prostate cancer, pancreatic cancer, head and neck cancer, lung cancer, non small-cell lung carcinoma, renal cancer, colorectal cancer, colon cancer, ovarian cancer, liver cancer and gastric cancer. 
     
     
         11 . The method of any one of the preceding claims, further comprising administering to the subject adjunct cancer therapy. 
     
     
         12 . The method of  claim 11 , wherein the adjunct cancer therapy is selected from the group consisting of chemotherapy, surgery, radiotherapy, thermotherapy, cancer vaccines, immunotherapy, gene therapy and laser therapy. 
     
     
         13 . The method of any one of the preceding claims, further comprising administering a further therapeutic agent selected from the group consisting of an MMP inhibitor, a chemotherapeutic agent, a growth inhibitory agent, a cancer vaccines, a gene therapy product, an immunotherapy and a cytokine. 
     
     
         14 . The method of any one of the preceding claims, wherein the cysteamine modulates enzymatic activity of a matrix metalloproteinase (MMP). 
     
     
         15 . The method of  claim 14 , wherein the enzymatic activity of the MMP is decreased in a primary tumor. 
     
     
         16 . The method of any of the preceding claims, wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof decreases metastatic nodules in the subject. 
     
     
         17 . The method of any of the preceding claims, wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof decreases ascites in the subject. 
     
     
         18 . The method of any one of the preceding claims, wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof is administered in a dose of about 10 mg/kg to about 250 mg/kg 
     
     
         19 . A method of decreasing matrix metalloproteinase (MMP) enzymatic activity in a cancer cell comprising contacting the cell with cysteamine, cystamine or pharmaceutically acceptable salts thereof in an amount effective to decrease MMP enzymatic activity in the cancer cell. 
     
     
         20 . The method of  claim 20  wherein the MMP is selected from the group consisting of MMP-1, MMP-2, MMP-3, MMP-4, MMP-5, MMP-6, MMP-6, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13 and MMP-14.