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.

What is claimed: 
     
         1 . A method of inhibiting or suppressing metastasis of a tumor in a mammalian subject comprising, administering cysteamine, cystamine or a pharmaceutically acceptable salt 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 a pharmaceutically acceptable salt thereof to the subject in an amount effective to treat the cancer. 
     
     
         3 . The method of  claim 1  wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof is administered orally. 
     
     
         4 . The method of  claim 1  Wherein the cysteamine, cystamine or pharmaceutically acceptable salt 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, cystamine, or pharmaceutically acceptable salt thereof 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  claim 1  wherein the cysteamine, cystamine far pharmaceutically acceptable salt thereof is administered less than four times a day. 
     
     
         7 . The method of  claim 1  wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof is administered twice a day. 
     
     
         8 . The method of  claim 1  wherein the administering results in increased thiol levels compared to levels before administration of the cysteamine, cystamine or pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 1  wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof is formulated in a tablet or capsule which is enterically coated. 
     
     
         10 . The method of  claim 1  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  claim 1  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 vaccination, immunotherapy, gene therapy and laser therapy. 
     
     
         13 . The method of  claim 1  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 vaccine, a gene therapy product, an immunotherapy and a cytokine. 
     
     
         14 . The method of  claim 1  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  claim 1  wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof decreases metastatic nodules in the subject. 
     
     
         17 . The method of  claim 1  wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof decreases ascites in the subject. 
     
     
         18 . The method of  claim 1  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 a pharmaceutically acceptable salt thereof in an amount effective to decrease MMP enzymatic activity in the cancer cell. 
     
     
         20 . The method of  claim 19  wherein the MMP is selected from the group consisting of MMP-I, MMP-Z, MMP-3, MMP-4, MMP-S, MMP-6, MMP-6, MMP-8, MMP-9, MMP-IO, MMP-I1, MMP-12, MMP-13 and MMP-14.