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;
providing a sample comprising a cell from the tumor;
detecting in the sample one or more of:
(i) a level of Ras-BRAF-MEK-Erk signaling;
(ii) dependence of growth or survival of the cell on Ras-BRAF-MEK-Erk signaling; or
(iii) expression of an activated or oncogenic BRAF or RAS;
determining that a cell of the tumor has increased Ras-BRAF-MEK-Erk signaling as compared to a predetermined reference level of 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, 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 IGFBP7 polypeptide consists of a polypeptide at least 80% identical to residues 29 to 282 of SEQ ID NO:1 or to SEQ ID NO:7.
9. The method of claim 8 , wherein the polypeptide is at least 85% identical to residues 29 to 282 of SEQ ID NO:1 or to SEQ ID NO:7.
10. 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 residues 29 to 282 of SEQ ID NO:1 or to SEQ ID NO:7.
11. The method of claim 10 , wherein the nucleic acid is in a viral vector.
12. The method of claim 11 , wherein the viral vector is an adenovirus, adeno-associated virus, retrovirus, or lentivirus vector.
13. The method of claim 1 , wherein the IGFBP7 polypeptide is administered topically, systemically, or locally.
14. The method of claim 13 , wherein the IGFBP7 polypeptide is administered locally by a drug-releasing implant.