Insulin-like growth factor binding protein 7 for treatment of cancer
Methods of treating a tumor in a subject include identifying a subject having, at risk for, or suspected of having a tumor, and administering to the subject an effective amount of an IGFBP7 agent if the tumor has increased Ras-BRAF-MEK-Erk signaling, is dependent for growth and/or survival upon the Ras-BRAF-MEK-Erk signaling pathway, and/or expresses an activated or oncogenic BRAF or RAS.
1. A method of treating a tumor in a subject, the method comprising:
identifying a subject having, at risk for, or suspected of having a tumor;
determining whether a cell of the tumor has increased Ras-BRAF-MEK-Erk signaling, is dependent for growth and/or survival upon the Ras-BRAF-MEK-Erk signaling pathway, and/or expresses an activated or oncogenic BRAF or RAS; and
administering to the subject an effective amount of an IGFBP7 agent if the tumor has increased Ras-BRAF-MEK-Erk signaling, is dependent for growth and/or survival upon the Ras-BRAF-MEK-Erk signaling pathway, and/or expresses an activated or oncogenic BRAF or RAS, thereby treating the tumor, wherein the IGFBP-7 agent comprises a polypeptide at least 80% identical to SEQ ID NO:7 or residues 29 to 282 SEQ ID NO:1.
2. The method of claim 1 , wherein the tumor is a cancer.
3. The method of claim 2 , wherein the cancer is a melanoma.
4. The method of claim 2 , wherein the cancer is a carcinoma, breast cancer, ovarian cancer, pancreatic cancer, colon cancer, colorectal carcinoma, or papillary thyroid carcinoma.
5. The method of claim 2 , wherein the cancer expresses an activated or oncogenic BRAF or RAS.
6. The method of claim 2 , wherein the activated or oncogenic BRAF is BRAFV600E.
7. The method of claim 1 , wherein the oncogenic BRAF is BRAFV600E.
8. The method of claim 1 , wherein the IGFBP7 agent comprises a polypeptide at least 90% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
9. The method of claim 8 , wherein the polypeptide is at least 95% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
10. The method of claim 8 , wherein the polypeptide is conjugated to a heterologous moiety.
11. The method of claim 10 , wherein the heterologous moiety is a heterologous polypeptide sequence.
12. The method of claim 1 , wherein the IGFBP7 agent consists of a polypeptide at least 90% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
13. The method of claim 12 , wherein the polypeptide is at least 95% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
14. The method of claim 13 , wherein the IGFBP7 agent is administered by introducing to the subject a nucleic acid encoding the polypeptide.
15. The method of claim 14 , wherein the nucleic acid is in a viral vector.
16. The method of claim 15 , wherein the viral vector is an adenovirus, adeno-associated virus, retrovirus, or lentivirus vector.
17. The method of claim 1 , wherein the IGFBP7 agent is administered topically, systemically, or locally.
18. The method of claim 17 , wherein the IGFBP7 agent is administered locally by a drug-releasing implant.
19. A method of inhibiting proliferation of a cell that has increased Ras-BRAF-MEK-Erk signaling, is dependent for growth and/or survival upon the Ras-BRAF-MEK-Erk signaling pathway, and/or expresses an activated or oncogenic BRAF or RAS, the method comprising administering to the cell an effective amount of an IGFBP7 agent, wherein the IGFBP-7 agent comprises a polypeptide at least 80% identical to SEQ ID NO:7 or residues 29 to 282 SEQ ID NO:1.
20. The method of claim 19 , wherein the cell is a tumor cell.
21. A method of treating a melanoma in a subject, the method comprising:
identifying a subject having, at risk for, or suspected of having a melanoma; and
administering to the subject an effective amount of an IGFBP7 agent, thereby treating the melanoma, wherein the IGFBP-7 agent comprises a polypeptide at least 80% identical to SEQ ID NO:7 or residues 29 to 282 SEQ ID NO:1.
22. The method of claim 21 , wherein the IGFBP7 agent comprises a polypeptide at least 90% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
23. The method of claim 22 , wherein the polypeptide is at least 95% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
24. The method of claim 22 , wherein the polypeptide comprises the sequence of SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
25. The method of claim 8 , wherein the polypeptide comprises the sequence of SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
26. The method of claim 12 , wherein the polypeptide consists of the sequence of SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
27. The method of claim 14 , wherein the IGFBP7 agent is administered by introducing to the subject a nucleic acid encoding a polypeptide comprising the sequence of SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
28. The method of claim 19 , wherein the IGFBP7 agent comprises a polypeptide at least 95% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
29. The method of claim 28 , wherein the polypeptide comprises the sequence of SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
30. The method of claim 1 , wherein the IGFBP7 agent comprises a polypeptide at least 85% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
31. The method of claim 19 , wherein the IGFBP7 agent comprises a polypeptide at least 85% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
32. The method of claim 1 , wherein the IGFBP7 agent comprises a polypeptide at least 90% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
33. The method of claim 21 , wherein the IGFBP7 agent comprises a polypeptide at least 85% identical to SEQ ID NO:7 or residues 29 to 282 of SEQ ID NO:1.
34. The method of claim 1 , wherein the IGFBP7 agent is administered by introducing to the subject a nucleic acid encoding the polypeptide.
35. The method of claim 12 , wherein the IGFBP7 agent is administered by introducing to the subject a nucleic acid encoding the polypeptide.