Methods of treating cancer by administering a soluble receptor comprising a human Fc domain and the Fri domain from human frizzled receptor
The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides a soluble FZD receptor comprising an extracellular domain of a human FZD receptor that inhibits growth of tumor cells. The present invention still further provides a soluble receptor comprising a Fri domain of a human FZD receptor that binds a ligand of a human FZD receptor and said soluble receptor is capable of inhibiting tumor growth. The present invention still further provides a method of treating cancer comprising administering a soluble FZD receptor comprising for example, either an extracellular domain of a human FZD receptor or a Fri domain of a human FZD receptor, in an amount effective to inhibit tumor growth.
1. A method of treating cancer in a human subject in need thereof, the method comprising administering to the subject a soluble receptor comprising (a) a fragment of an extracellular domain of a human Frizzled (FZD) receptor and (b) a human Fc domain, wherein:
(i) the fragment of the extracellular domain of the human FZD receptor consists essentially of the Fri domain of the human FZD receptor;
(ii) the soluble receptor has a longer half-life in vivo than a soluble receptor comprising the extracellular domain of the FZD receptor and the human Fc, domain; and
(iii) the cancer is selected from the group consisting of pancreatic cancer, ovarian cancer, hepatocellular cancer, breast cancer, colorectal cancer, lung cancer, prostate cancer, and head and neck cancer.
2. The method of claim 1 , wherein the cancer is selected from the group consisting of ovarian cancer, pancreatic cancer, and hepatocellular cancer.
3. The method of claim 1 , wherein the Fri domain of the human FZD receptor comprises the Fri domain of FZD4, FZD5, or FZD8.
4. The method of claim 3 , wherein the Fri domain of the human FZD receptor comprises the Fri domain of FZD8.
5. The method of claim 4 , wherein the Fri domain of human FZD8 comprises the amino acids from approximately 28 to 158 of the amino acid sequence of SEQ NO:7.
6. The method of claim 5 , wherein the human Fe domain is human IgG1 Fc comprising the amino acid sequence of SEQ ID NO:4.
7. The method of claim 6 , wherein the cancer is ovarian cancer.
8. The method of claim 7 , wherein the soluble receptor is administered with chemotherapy.
9. The method of claim 8 , wherein the chemotherapy includes one or more of paclitaxel, cisplatin, and carboplatin.
10. The method of claim 9 , wherein the chemotherapy includes paclitaxel and carboplatin.
11. The method of claim 6 , wherein the cancer is pancreatic cancer.
12. The method of claim 11 , wherein the soluble receptor is administered with chemotherapy.
13. The method of claim 6 , wherein the cancer is hepatocellular cancer.
14. The method of claim 13 , wherein the soluble receptor is administered with chemotherapy.
15. A method of treating cancer in a human subject in need thereof, the method comprising administering to the subject a soluble receptor comprising a polypeptide that consists of (a) a fragment of an extracellular domain of a human Frizzled (FZD) receptor and (b) a human Fc domain, wherein:
(i) the fragment of the extracellular domain of the human FZD receptor consists essentially of the Fri domain of the human FZD receptor;
(ii) the cancer is selected from the group consisting of pancreatic cancer, ovarian cancer, hepatocellular cancer, breast cancer, colorectal cancer, lung cancer, prostate cancer, and head and neck cancer.
16. The method of claim 15 , wherein the cancer is selected from the group consisting of ovarian cancer, pancreatic cancer, and hepatocellular cancer.
17. The method of claim 15 , wherein the Fri domain of the human FZD receptor comprises the Fri domain of FZD4, FZD5, or FZD8.
18. The method of claim 17 , wherein the Fri domain of the human FZD receptor comprises the Fri domain of FZD8.
19. The method of claim 18 , wherein the Fri domain of human FZD8 comprises the amino acids from approximately 28 to 158 of the amino acid sequence of SEQ ID NO:7.
20. The method of claim 19 , wherein the human Fc domain is human IgG1 Fc comprising the amino acid sequence of SEQ ID NO:4.
21. The method of claim 20 , wherein the cancer is ovarian cancer.
22. The method of claim 21 , wherein the soluble receptor is administered with chemotherapy.
23. The method of claim 22 , wherein the chemotherapy includes one or more of paclitaxel, cisplatin, and carboplatin.
24. The method of claim 23 , wherein the chemotherapy includes paclitaxel and carboplatin.
25. The method of claim 20 , wherein the cancer is pancreatic cancer.
26. The method of claim 25 , wherein the soluble receptor is administered with chemotherapy.
27. The method of claim 20 , wherein the cancer is hepatocellular cancer.
28. The method of claim 27 , wherein the soluble receptor is administered with chemotherapy.