Treatment and diagnosis of melanoma
The present invention discloses novel agents and methods for diagnosis and treatment of melanoma. Also disclosed are related arrays, kits, and screening methods.
1. A method of treating metastatic cancer in a subject in need thereof, the method comprising administering to the subject an LXRβ agonist selected from:
or a pharmaceutically acceptable salt thereof, in an amount sufficient to suppress progression of the metastatic cancer, wherein the metastatic cancer is breast cancer, lung cancer, bladder cancer, head and neck cancer, renal cell cancer, colorectal cancer, lymphoma, hepatocellular carcinoma, or prostate cancer.
2. The method of claim 1 , wherein the metastatic cancer is breast cancer.
3. The method of claim 2 , wherein the breast cancer is triple negative breast cancer.
4. The method of claim 1 , wherein the metastatic cancer is lung cancer.
5. The method of claim 4 , wherein the lung cancer is non-small cell lung cancer.
6. The method of claim 4 , wherein the lung cancer is small cell lung cancer.
7. The method of claim 1 , wherein the metastatic cancer is bladder cancer.
8. The method of claim 1 , wherein the metastatic cancer is head and neck cancer.
9. The method of claim 1 , wherein the metastatic cancer is renal cell cancer.
10. The method of claim 1 , wherein the metastatic cancer is colorectal cancer.
11. The method of claim 1 , wherein the metastatic cancer is lymphoma.
12. The method of claim 1 , wherein the metastatic cancer is hepatocellular carcinoma.
13. The method of claim 1 , wherein the metastatic cancer is prostate cancer.
14. The method of claim 1 , wherein the LXRβ agonist is compound 1, or a pharmaceutically acceptable salt thereof.
15. The method of claim 1 , wherein the LXRβ agonist is compound 2, or a pharmaceutically acceptable salt thereof.
16. The method of claim 1 , wherein the LXRβ agonist is compound 12, or a pharmaceutically acceptable salt thereof.
17. The method of claim 1 , wherein the LXRβ agonist is compound 25, or a pharmaceutically acceptable salt thereof.
18. The method of claim 1 , wherein the metastatic cancer is drug resistant.
19. The method of claim 18 , wherein the metastatic cancer is resistant to platinum-containing chemotherapy, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, an IDO inhibitor, an anti-hormonal therapy, an antimitotic agent, an angiogenesis inhibitor, and/or a kinase inhibitor.
20. The method of claim 18 , wherein the metastatic cancer progressed on or after treatment with platinum-containing chemotherapy, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, an IDO inhibitor, an anti-hormonal therapy, an antimitotic agent, an angiogenesis inhibitor, and/or a kinase inhibitor.
21. The method of claim 18 , wherein the metastatic cancer has been determined to be, or is predicted to be, resistant to platinum-containing chemotherapy, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, an IDO inhibitor, an anti-hormonal therapy, an antimitotic agent, an angiogenesis inhibitor, and/or a kinase inhibitor.
22. The method of claim 1 , wherein the method does not comprise further concurrently administering to the subject an antiproliferative agent.
23. The method of claim 1 , wherein the method further comprises administration of an additional anticancer therapy.
24. The method of claim 23 , wherein the additional anticancer therapy is a platinum-containing chemotherapy, an immunomodulatory, an anti-hormonal therapy, an antimitotic agent, an angiogenesis inhibitor, and/or a kinase inhibitor.
25. The method of claim 24 , wherein the platinum-containing chemotherapy is oxaliplatin, carboplatin, or cisplatin, the immunomodulator is a PD-1 inhibitor, a CTLA4 inhibitor, an IDO inhibitor, and/or a PDL1 inhibitor, the kinase inhibitor is erlotinib or trastuzumab, the angiogenesis inhibitor is bevacizumab, and/or the antimitotic agent is paclitaxel or docetaxel.
26. The method of claim 1 , wherein the method comprises reducing or stopping the formation of new metastatic tumors and/or reducing, stopping, or reversing the load of a metastatic tumor.
27. The method of claim 3 , wherein the method comprises the suppression of metastatic colonization of the metastatic cancer.
28. The method of claim 10 , wherein the method comprises the suppression of metastatic colonization of the metastatic cancer to the lung and/or the brain.