Cancer therapy
The present invention provides agents useful in the treatment of cancer, as well as systems for identifying and/or characterizing such agents, and systems for identifying and/or characterizing patient populations responsive to particular agents.
1. A method of treating cancer by administering to a patient in need thereof an agent that directly inhibits activity of a RAS palmitoyl-acyl transferase and reduces palmitoylation of NRAS, wherein the agent blocks a RAS palmitoylation site.
2. The method of claim 1 , wherein the cancer is associated with an oncogene that acts upstream of RAS.
3. The method of claim 1 or claim 2 , wherein the cancer is not associated with a mutation of NRAS.
4. A method of treating cancer by administering to a patient in need thereof an agent that directly inhibits activity of a RAS palmitoyl-acyl transferase and reduces palmitoylation of NRAS, wherein the agent comprises a RAS polypeptide variant that dominantly suppresses palmitoylation of an oncogenic RAS.
5. The method of claim 1 , wherein the RAS palmitoyl-acyl transferase is selected from the group consisting of SEQ ID NO: 2-25 and combinations thereof.
6. The method of claim 4 , wherein the RAS polypeptide variant comprises at least one non-natural amino acid.
7. The method of claim 4 , wherein the cancer is associated with an oncogene that acts upstream of RAS.
8. The method of claim 4 or 7 , wherein the cancer is not associated with a mutation of NRAS.
9. The method of claim 4 , wherein the RAS palmitoyl-acyl transferase is selected from the group consisting of SEQ ID NO: 2-25 and combinations thereof.