Markers for and methods of targeting tumor stem cells
AssigneeWhitehead Institute for Biomedical Research
InventorsTan A. Ince, Tong Ihn Lee, Richard A. Young
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Abstract
The invention provides methods of targeting tumor stem cells that comprise inhibiting the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. The invention further provides methods for identifying tumor stem cells comprising detecting increased levels and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. Further provided are kits and articles of manufacture comprising inhibitors of the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. Methods for screening for inhibitors of the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7 are also provided.
Claims18
A method for inhibiting the proliferation of or eliminating one or more epithelial carcinoma tumor stem cells that express HDAC1 and/or HDAC7 comprising contacting said one or more cells with an effective amount of at least one inhibitor of HDAC1 and/or an effective amount of at least one inhibitor of HDAC7, wherein an epithelial carcinoma tumor stem cell sample obtained from a source of said one or more cells has been determined to have an increased level or activity of HDAC1 protein and/or an increased level or activity of HDAC7 protein as compared to a standard level.
A method for treating a tumor comprising epithelial carcinoma tumor stem cells that express HDAC1 and/or HDAC7, the method comprising:
- administering to an individual in need of treatment for said tumor an effective amount of an agent which specifically inhibits the level and/or activity of HDAC1 and/or HDAC7 protein, wherein an epithelial carcinoma tumor stem cell sample obtained from said tumor has been determined to have an increased level or activity of HDAC1 protein and/or an increased level or activity of HDAC7 protein as compared to a standard level.
A method comprising contacting one or more ovarian epithelial carcinoma tumor stem cells that express higher levels of (i) HDAC1 protein and/or (ii) HDAC7 protein, and/or (iii) phosphorylated HDAC7 protein compared to non-stem tumor cells in the tumor cell population from which the one or more ovarian epithelial carcinoma tumor stem cells are obtained with an effective amount of at least one inhibitor of HDAC1 and/or an effective amount of at least one inhibitor of HDAC7, wherein the level of HDAC1 protein and/or HDAC7 protein and/or phosphorylated HDAC7 protein in the one or more ovarian epithelial carcinoma tumor stem cells is decreased, thereby inhibiting the proliferation of or eliminating the one or more ovarian epithelial carcinoma tumor stem cells.
A method comprising contacting one or more breast epithelial carcinoma tumor stem cells that express higher levels of (i) HDAC1 protein and/or (ii) HDAC7 protein, and/or (iii) phosphorylated HDAC7 protein compared to non-stem tumor cells in the tumor cell population from which the one or more breast epithelial carcinoma tumor stem cells are obtained with an effective amount of at least one inhibitor of HDAC1 and/or an effective amount of at least one inhibitor of HDAC7, wherein the level of HDAC1 protein and/or HDAC7 protein and/or phosphorylated HDAC7 protein in the one or more breast epithelial carcinoma tumor stem cells is decreased, thereby inhibiting the proliferation of or eliminating the one or more breast epithelial carcinoma tumor stem cells.
Dependencies are inferred from the claim text.