Methods of treating cancer with a combination of selected MEK1/2 and AXL inhibitors
Methods, compounds and kits relating to treating cancer, reducing kinase inhibitor or resistance, and reducing or preventing diminished ectodomain shedding are described.
1. A method of treating a cancer in an individual comprising administering a therapeutically effective amount of a MEK1/2 inhibitor and an AXL inhibitor,
wherein the MEK1/2 inhibitor is selected from the group consisting of PD325901, AZD6244 (selumetinib), and trametinib (GSK1120212): and
wherein the AXL inhibitor is selected from the group consisting of R428, MP-470 (amuvatinib), and XL-880 (foretinib).
2. The method of claim 1 , further comprising administering an additional therapeutic agent.
3. A method of treating a cancer in an individual comprising administering a therapeutically effective amount of a MEK1/2 inhibitor, an AXL inhibitor and a tissue inhibitor of metalloproteinase 1 (TIMP1) inhibitor.
4. The method of claim 3 , wherein the tissue inhibitor of metalloproteinase 1 (TIMP1) inhibitor is a TIMP1 neutralizing antibody.
5. The method of claim 1 , wherein the cancer is a carcinoma, sarcoma, lymphoma, leukemia, or blastoma.
6. The method of claim 5 , wherein the carcinoma is a breast cancer, a melanoma, a lung cancer or an ovarian cancer.
7. The method of claim 6 , wherein the breast cancer expresses low estrogen receptor, progesterone receptor, HER2, or a combination thereof triple-negative breast cancer (TNBC).
8. The method of claim 5 , wherein the blastoma is glioblastoma multiforme.
9. The method of claim 1 , wherein the MEK1/2 inhibitor is administered to the individual at or near the same time as the AXL inhibitor.
10. The method of claim 1 , wherein the MEK1/2 inhibitor is administered before or after administration of the AXL inhibitor to the individual.
11. The method of claim 1 , wherein the MEK1/2 inhibitor and the AXL inhibitor are administered to the individual in a single formulation.
12. The method of claim 1 , wherein the MEK1/2 inhibitor and the AXL inhibitor are administered to the individual in different formulations.
13. The method of claim 1 , wherein administering the MEK1/2 inhibitor and AXL inhibitor reduces tumor growth in the individual.
14. The method of claim 1 , wherein administering the MEK1/2 inhibitor and AXL inhibitor reduces metastasis in the individual.
15. A method of treating a cancer in an individual comprising administering a therapeutically effective amount of a MEK inhibitor, an AXL inhibitor, and a BRAF inhibitor,
wherein the MEK1/2 inhibitor is selected from the group consisting of PD325901, AZD6244 (selumetinib), and trametinib (GSK1120212); and
wherein the AXL inhibitor is selected from the group consisting of R428, MP-470 (amuvatinib), and XL-880 (foretinib).
16. The method of claim 1 , wherein the AXL inhibitor is R428.
17. The method of claim 1 , wherein the MEK1/2 inhibitor is PD325901 or AZD6244 (selumetinib).
18. The method of claim 15 , wherein the MEK1/2 inhibitor is PD325901 or AZD6244 (selumetinib).
19. The method of claim 1 , wherein the MEK1/2 inhibitor is PD325901 or AZD6244 (selumetinib) and wherein the AXL inhibitor is R428.
20. The method of claim 15 , wherein the AXL inhibitor R428.
21. The method of claim 15 , wherein the MEK1/2 inhibitor is PD325901 or AZD6244 (selumetinib) and wherein the AXL inhibitor is R428.