Methods for targeting cancer stem cells
The invention provides naphthofuran compounds, polymorphs of naphthofuran compounds, naphthofuran compounds in particle form, purified compositions that contain one or more naphthofuran compounds, purified compositions that contain one or more naphthofuran compounds in particle form, methods of producing these naphthofuran compounds, polymorphs, purified compositions and/or particle forms, and methods of using these naphthofuran compounds, polymorphs, purified compositions and/or particle forms to treat subjects in need thereof.
1. A method for treating a cancer in a human subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound having the structure
or a pharmaceutically acceptable salt or hydrate thereof,
wherein the compound is administered orally to the subject at a total daily dose in a range of from about 20 mg to about 1000 mg, and
the compound is in the form of crystalline particles, the particles having diameters of from about 0.002 μm to about 200 μm.
2. The method of claim 1 , wherein the compound is administered to the subject at a total daily dose in a range of from about 400 mg to about 1000 mg.
3. The method of claim 1 , wherein the compound is administered to the subject in a single daily dose in a range of from about 20 mg to about 1000 mg.
4. The method of claim 1 , wherein the compound is administered to the subject in two daily doses.
5. The method of claim 4 , wherein each dose is in a range of from about 200 mg to about 500 mg.
6. The method of claim 4 , wherein each dose is about 500 mg.
7. The method of claim 1 , wherein the compound is administered to the subject in three daily doses.
8. The method of claim 7 , wherein each dose is in a range of from about 200 mg to about 500 mg.
9. The method of claim 1 , wherein the compound is administered orally in conjunction with milk on an empty stomach.
10. The method of claim 1 , wherein the particles have diameters of equal to or less than about 20 μm.
11. The method of claim 1 , wherein the compound is in a pharmaceutical composition comprising a population of particles of the compound, and a fraction of the cumulative total of the particles have a diameter in the range of about 0.2 μm to about 20 μm.
12. The method of claim 1 , wherein the compound is in a pharmaceutical composition comprising a population of particles of the compound, and 50% of the cumulative total of the particles (D 50 ) have a diameter of about 2 μm.
13. The method of claim 1 , wherein the compound is administered in a purified composition having a purity greater than or equal to about 95.0%.
14. The method of claim 1 , wherein the cancer is colorectal cancer, breast cancer, ovarian cancer, head and neck cancer, melanoma, angiosarcoma, gastric adenocarcinoma, pancreatic cancer, gastroesophageal junction (GEJ) cancer, gastric cancer, esophageal cancer, leukemia, lymphoma, multiple myeloma, brain tumor, hepatocellular carcinoma, lung cancer, prostate cancer, bile duct cancer, endometrial cancer, bladder cancer, renal cancer, or adrenocorticoid cancer.
15. The method of claim 1 , wherein the cancer is colorectal cancer.
16. The method of claim 1 , wherein the cancer is ovarian cancer.
17. The method of claim 1 , wherein the cancer is breast cancer.
18. The method of claim 1 , wherein the cancer is lung cancer.
19. The method of claim 1 , wherein the cancer is refractory cancer.
20. The method of claim 1 , wherein the cancer is recurrent cancer.
21. The method of claim 1 , wherein the cancer is metastatic cancer.
22. The method of claim 1 , wherein the cancer is associated with the expression of activated STAT3.
23. The method of claim 1 , the method further comprising detecting a level of activated STAT3, where the level of activated STAT3 expression is used as a biomarker for patient selection.
24. The method of claim 1 , wherein the cancer is gastroesophageal junction (GEJ) cancer.
25. The method of claim 1 , wherein the cancer is hepatocellular carcinoma.
26. The method of claim 1 , wherein the cancer is melanoma.
27. The method of claim 1 , wherein the cancer is brain tumor.
28. The method of claim 1 , wherein the cancer is leukemia, lymphoma, or multiple myeloma.
29. The method of claim 1 , wherein the cancer is pancreatic cancer.
30. The method of claim 1 , wherein the cancer is a sarcoma.
31. The method of claim 1 , wherein the cancer is a carcinoma.
32. The method of claim 1 , wherein the cancer is a hematological malignancy.
33. The method of claim 1 comprising administering one or more unit dosage forms of the compound.
34. The method of claim 33 , wherein each unit dosage form comprises about 20 mg of the compound.
35. The method of claim 33 , wherein each unit dosage form comprises about 40 mg of the compound.
36. The method of claim 33 , wherein each unit dosage form comprises about 50 mg of the compound.
37. The method of claim 33 , wherein each unit dosage form comprises about 80 mg of the compound.