Wnt antagonist and methods of treatment and screening
The present invention relates to compositions comprising Wnt antagonists and methods of treating Wnt-associated diseases and disorders, such as cancer, inducing differentiation, and reducing the frequency of cancer stem cells, as well as novel methods of screening for such Wnt antagonists. In particular, the invention discloses soluble FZD, SFRP and Ror receptors and their use.
1. A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of a Wnt-binding agent that comprises a polypeptide comprising the amino acid sequence of SEQ ID NO:53.
2. The method of claim 1 , wherein the Wnt-binding agent is present in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
3. The method of claim 1 , wherein the cancer is selected from the group consisting of colorectal cancer, pancreatic cancer, breast cancer, lung cancer, ovarian cancer, liver cancer, kidney cancer, prostate cancer, gastrointestinal cancer, melanoma, cervical cancer, bladder cancer, glioblastoma, and head and neck cancer.
4. The method of claim 1 , wherein the method further comprises administering to the subject a second therapeutic agent.
5. The method of claim 4 , wherein the second therapeutic agent is a chemotherapeutic agent.
6. The method of claim 1 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.
7. The method of claim 1 , wherein the cancer is pancreatic cancer.
8. The method of claim 7 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.
9. The method of claim 7 , wherein the method further comprises administering to the subject a chemotherapeutic agent.
10. The method of claim 9 , wherein the chemotherapeutic agent is an anti-metabolite.
11. The method of claim 10 , wherein the anti-metabolite is selected from the group consisting of gemcitabine, fluorouracil, capecitabine, methotrexate sodium, ralitrexed, pemetrexed, tegafur, cytosine arabinoside, thioguanine, 5-azacytidine, 6-mercaptopurine, azathioprine, 6-thioguanine, pentostatin, fludarabine phosphate, and cladribine.
12. The method of claim 11 , wherein the anti-metabolite is gemcitabine.
13. The method of claim 12 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.
14. The method of claim 9 , wherein the chemotherapeutic agent is a taxane.
15. The method of claim 14 , wherein the taxane is selected from the group consisting of paclitaxel, nab-paclitaxel, docetaxel, DHA-paclitaxel, and PG-paclitaxel.
16. The method of claim 15 , wherein the taxane is nab-paclitaxel.
17. The method of claim 16 , wherein the method further comprises administering to the subject gemcitabine.
18. The method of claim 17 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.
19. The method of claim 1 , wherein the cancer is ovarian cancer.
20. The method of claim 19 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.
21. The method of claim 19 , wherein the method further comprises administering to the subject a chemotherapeutic agent.
22. The method of claim 21 , wherein the chemotherapeutic agent is a taxane.
23. The method of claim 22 , wherein the taxane is paclitaxel, nab-paclitaxel, docetaxel, DHA-paclitaxel, or PG-paclitaxel.
24. The method of claim 23 , wherein the taxane is paclitaxel.
25. The method of claim 21 , wherein the chemotherapeutic agent is a platinum complex.
26. The method of claim 25 , wherein the platinum complex is cisplatin or carboplatin.
27. The method of claim 26 , wherein the platinum complex is carboplatin.
28. The method of claim 27 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.
29. The method of claim 27 , wherein the method further comprising administering to the subject paclitaxel.
30. The method of claim 29 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.
31. The method of claim 1 , wherein the cancer is liver cancer.
32. The method of claim 31 , wherein the cancer is hepatocellular cancer.
33. The method of claim 32 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.
34. The method of claim 32 , wherein the method further comprises administering to the subject a chemotherapeutic agent.
35. The method of claim 34 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:53.