Treatment and diagnosis of melanoma

Patent metadata

Field	Value
Publication number	US-9707195-B2
Application number	US-201615228643-A
Country	US
Kind code	B2
Filing date	Aug 4, 2016
Priority date	Aug 13, 2012
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

The present invention discloses novel agents and methods for diagnosis and treatment of melanoma. Also disclosed are related arrays, kits, and screening methods.

First claim

The invention claimed is:

1. A method of treating cancer in a subject in need thereof, wherein the cancer is resistant to a PD-1 inhibitor, a PD-L1 inhibitor, and/or a CTLA-4 inhibitor, the method comprising administering to the subject an effective amount of an LXRβ agonist, or a pharmaceutically acceptable salt thereof, and a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitor, wherein the LXRβ agonist is:

or a pharmaceutically acceptable salt thereof,
wherein the cancer is ovarian cancer, breast cancer, lung cancer, glioblastoma, melanoma, bladder cancer, head and neck cancer, renal cell cancer, colorectal cancer, lymphoma, leukemia, multiple myeloma, or hepatocellular carcinoma.

2. The method of claim 1 , wherein the cancer is breast cancer, ovarian cancer, lung cancer, glioblastoma, or melanoma.

3. The method of claim 1 , wherein the cancer is ovarian cancer.

4. The method of claim 3 , wherein the ovarian cancer is also resistant to platinum agents.

5. The method of claim 1 , wherein the cancer is breast cancer.

6. The method of claim 5 , wherein the breast cancer is triple negative breast cancer.

7. The method of claim 1 , wherein the cancer is lung cancer.

8. The method of claim 7 , wherein the lung cancer is non-small cell lung cancer.

9. The method of claim 1 , wherein the cancer is glioblastoma.

10. The method of claim 1 , wherein the cancer is melanoma.

11. The method of claim 10 , wherein the melanoma is also resistant to dacarbazine, a BRAF inhibitor, and/or a MEK inhibitor.

12. The method of claim 1 , wherein the cancer is bladder cancer.

13. The method of claim 1 , wherein the cancer is head and neck cancer.

14. The method of claim 1 , wherein the cancer is renal cell cancer.

15. The method of claim 1 , wherein the cancer is colorectal cancer.

16. The method of claim 1 , wherein the cancer is lymphona.

17. The method of claim 1 , wherein the cancer is leukemia.

18. The method of claim 1 , wherein the cancer is multiple myeloma.

19. The method of claim 1 , wherein the cancer is hepatocellular carcinoma.

20. The method of claim 1 , wherein the LXRβ agonist is compound 1, or a pharmaceutically acceptable salt thereof.

21. The method of claim 1 , wherein the LXRβ agonist is compound 2, or a pharmaceutically acceptable salt thereof.

22. The method of claim 1 , wherein the LXRβ agonist is compound 12, or a pharmaceutically acceptable salt thereof.

23. The method of claim 1 , wherein the LXRβ agonist is compound 25, or a pharmaceutically acceptable salt thereof.

24. The method of claim 1 , wherein the cancer is metastatic.

25. The method of claim 24 , wherein the LXRβ agonist is administered in an amount sufficient to increase the expression level or activity level of ApoE to a level sufficient to suppress metastatic progression of the cancer.

26. The method of claim 1 , wherein the LXRβ agonist, or a pharmaceutically acceptable salt thereof, and the PD-1 inhibitor or PD-L1 inhibitor are administered within 28 days of each other.

27. The method of claim 1 , wherein the cancer progressed on or after treatment with a PD-1 inhibitor, a PD-L1 inhibitor, and/or a CTLA-4 inhibitor.

28. The method of claim 1 , wherein the cancer has been determined to be, or is predicted to be resistant to a PD-1 inhibitor, a PD-L1 inhibitor, and/or a CTLA-4 inhibitor.

Assignees

• Univ Rockefeller

Inventors

• Tavazoie Sohail F
• Pencheva Nora

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title