Melanoma chemoprevention

Abstract

Disclosed herein are methods and uses for preventing melanoma, reducing progression of atypical nevi, and inducing cell cycle arrest and/or apoptosis in a melanoma cell through oral and enteral administration of sulforaphane to subjects indicated to be at risk due to factor(s) such as medical history of atypical nevi, melanoma, or UV exposure. Sulforaphane can be administered orally as a safe and well-tolerated natural agent as a chemopreventive strategy in individuals with atypical melanocytic nevi.

We claim: 
     
         1 . A method of preventing progression of atypical nevi in a subject, comprising administering orally to a subject having atypical nevi a therapeutically effective amount of a pharmaceutical composition comprising sulforaphane, thereby reducing progression of the atypical nevi. 
     
     
         2 . A method of preventing melanoma in a subject, comprising administering orally to a subject a therapeutically effective amount of a pharmaceutical composition comprising sulforaphane, thereby preventing melanoma in the subject. 
     
     
         3 . The method of  claim 1 , wherein preventing progression comprises preventing emergence of additional atypical nevi in the subject. 
     
     
         4 . The method of  claim 1 , wherein preventing progression comprises preventing transition of atypical nevi from morphologically less atypical to morphologically more atypical on a tiered scale. 
     
     
         5 . The method of  claim 1 , comprising administering the sulforaphane as a tea or as a gel capsule. 
     
     
         6 . The method of  claim 1 , comprising administering about 50 to about 400 μM of sulforaphane. 
     
     
         7 . The method of  claim 1 , comprising administering about 0.5 to about 10 μM of sulforaphane per kilogram of bodyweight of the subject. 
     
     
         8 . The method of  claim 1 , comprising administering about 50, about 100, or about 200 μM of sulforaphane. 
     
     
         9 . The method of  claim 1 , comprising administering about 0.5, about 2.0, or about 4.0 μM of sulforaphane per kilogram of bodyweight of the subject. 
     
     
         10 . The method of  claim 1 , comprising administering the sulforaphane in repeated doses. 
     
     
         11 . The method of  claim 1 , comprising administering the sulforaphane thrice daily, twice daily, daily, bi-weekly, or weekly. 
     
     
         12 . The method of  claim 1 , wherein administering is repeated over about 10 days to about 6 months. 
     
     
         13 . The method of  claim 2 , wherein the subject has a family history of melanoma or dysplastic nevi syndrome. 
     
     
         14 . The method of  claim 1 , wherein the subject has two or more atypical nevi. 
     
     
         15 . The method of  claim 1 , wherein the subject has two or more atypical nevi that are greater than 4 millimeters in diameter. 
     
     
         16 . The method of  claim 1 , wherein the subject has two or more atypical nevi, and wherein one or more of the nevi have been morphologically classified on a tiered scale. 
     
     
         17 . The method of  claim 2 , wherein the subject has a loss of function mutation in an MC1R gene. 
     
     
         18 . The method of  claim 1 , further comprising measuring STAT1 or STAT3 expression in a sample from the subject. 
     
     
         19 . The method of  claim 18 , wherein the sample is a biopsy. 
     
     
         20 . The method of  claim 19 , wherein measuring STAT1 or STAT3 expression comprises measuring with an immunoassay. 
     
     
         21 . The method of  claim 1 , wherein the subject has a loss of function mutation in an MC1R gene.