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 a tumor that has a cell having 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 polypeptide at least 80% identical to SEQ ID NO:1 or SEQ ID NO:7, thereby treating the tumor.
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 polypeptide is at least 85% identical to SEQ ID NO:1 or SEQ ID NO:7.
9. The method of claim 1 , wherein the polypeptide is conjugated to a heterologous moiety.
10. The method of claim 9 , wherein the heterologous moiety is a heterologous polypeptide sequence.
11. The method of claim 1 , wherein the IGFBP7 agent consists of a polypeptide at least 80% identical to SEQ ID NO:1 or SEQ ID NO:7.
12. The method of claim 11 , wherein the polypeptide is at least 85% identical to SEQ ID NO:1 or SEQ ID NO:7.
13. The method of claim 1 , wherein the IGFBP7 polypeptide is administered by introducing to the subject a nucleic acid encoding a polypeptide at least 85% identical to SEQ ID NO:1 or SEQ ID NO:7.
14. The method of claim 13 , wherein the nucleic acid is in a viral vector.
15. The method of claim 14 , wherein the viral vector is an adenovirus, adeno-associated virus, retrovirus, or lentivirus vector.
16. The method of claim 1 , wherein the IGFBP7 agent is administered topically, systemically, or locally.
17. The method of claim 16 , wherein the IGFBP7 agent is administered locally by a drug-releasing implant.
18. 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
identifying 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; and
administering to the cell an effective amount of an IGFBP7 polypeptide.
19. The method of claim 18 , wherein the cell is a tumor cell.
20. 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 polypeptide at least 80% identical to SEQ ID NO:1 or SEQ ID NO:7, thereby treating the melanoma.