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 a derivative 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 pancreatic cancer in a human subject comprising administering cysteamine, cystamine or a pharmaceutically acceptable salt thereof to the subject in an amount effective to inhibit metastasis of the cancer, but less than an amount cytotoxic to the cancer, and wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof is administered at a daily dose of at least 10 mg/kg. 
     
     
         2 . A method of reducing metastasis of pancreatic cancer in a human subject comprising administering cysteamine, cystamine or a pharmaceutically acceptable salt thereof to the subject in an amount effective to reduce metastasis of the cancer, which amount is less than an amount cytotoxic to 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 or 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  further comprising administering to the subject adjunct cancer therapy. 
     
     
         11 . The method of  claim 10 , wherein the adjunct cancer therapy is selected from the group consisting of chemotherapy, surgery, radiotherapy, thermotherapy, cancer vaccination, immunotherapy, gene therapy and laser therapy. 
     
     
         12 . 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. 
     
     
         13 . The method of  claim 1  wherein the cysteamine modulates enzymatic activity of a matrix metalloproteinase (MMP). 
     
     
         14 . The method of  claim 13 , wherein the enzymatic activity of the MMP is decreased in a primary tumor. 
     
     
         15 . The method of  claim 1  wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof decreases metastatic nodules in the subject. 
     
     
         16 . The method of  claim 1  wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof decreases ascites in the subject. 
     
     
         17 . The method of  claim 1  wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof is administered in a dose up to about 250 mg/kg. 
     
     
         18 . A method of decreasing matrix metalloproteinase (MMP) enzymatic activity in a human pancreatic cancer cell comprising contacting the cancer cell with cysteamine, cystamine or a pharmaceutically acceptable salt thereof in an amount effective to decrease MMP enzymatic activity in the cancer cell. 
     
     
         19 . The method of  claim 18  wherein the MMP is selected from the group consisting of MMP-1, MMP-2, MMP-3, MMP-4, MMP-5, MMP-6, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13 and MMP-14. 
     
     
         20 . A method of reducing metastasis in a human patient afflicted with pancreatic cancer comprising administering to the patient an amount of cysteamine, cystamine, or pharmaceutically acceptable salt thereof in an amount effective to reduce metastasis of the cancer, the amount being less than an amount cytotoxic to the cancer, to reduce metastasis of the cancer. 
     
     
         21 . The method of  claim 20 , wherein the administration is prior to surgery, to prevent metastasis. 
     
     
         22 . A method of prolonging survival in a human patient afflicted with pancreatic cancer comprising administering to the patient an amount of cysteamine, cystamine, or pharmaceutically acceptable salt thereof in an amount effective to prolong survival of the patient, the amount being less than an amount cytotoxic to the cancer. 
     
     
         23 . The method of  claim 1 , wherein the cysteamine, cystamine or pharmaceutically acceptable salt thereof is conjugated with nanoparticles.