Melanoma chemoprevention

• US 9,393,225 B2
• Filed: 05/03/2013
• Issued: 07/19/2016
• Est. Priority Date: 05/04/2012
• Status: Active Grant

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Beumer, Jan H., Kirkwood, John M., Singh, Shivendra V., Brown, Charles K.
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US14/398,713
• Publication Number:
  US 20150141507A1
• Time in Patent Office: 1,173 Days
• Field of Search: 514/514
• US Class Current: 1/1
• CPC Class Codes: A61K 31/26 Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: G01N 2333/4706 stimulating, promoting or activating activity
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

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.

Claims

1. A method of reducing 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.

3. The method of claim 1, wherein reducing progression comprises reducing emergence of additional atypical nevi in the subject.

4. The method of claim 1, wherein reducing progression comprises reducing 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 μ

M of sulforaphane.

7. The method of claim 1, comprising administering about 0.5 to about 10 μ

M of sulforaphane per kilogram of bodyweight of the subject.

8. The method of claim 1, comprising administering about 50, about 100, or about 200 μ

M of sulforaphane.

9. The method of claim 1, comprising administering about 0.5, about 2.0, or about 4.0 μ

M 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.

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.

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 STAT3expression comprises an immunoassay.

2. A method of treating a melanoma in a subject, comprising administering orally to a subject a therapeutically effective amount of a pharmaceutical composition comprising sulforaphane, thereby treating the melanoma in the subject.

13. The method of claim 2, wherein the subject has a family history of melanoma or dysplastic nevi syndrome.

17. The method of claim 2, wherein the subject has a loss of function mutation in an MC1R gene.

22. The method of claim 2, wherein treating the melanoma comprises reducing transition of an atypical nevus of the melanoma from morphologically less atypical to morphologically more atypical on a tiered scale.

21. A method of inducing cell cycle arrest and/or apoptosis of a melanoma cell, comprising:

administering orally to a subject a pharmaceutical composition comprising sulforaphane, thereby inducing cell cycle arrest and/or apoptosis of the melanoma cell; and

measuring the cell cycle arrest and/or apoptosis of the melanoma cell.