Methods for overcoming glucocorticoid resistance and for determining glucocorticoid resistance potential in cancer
First Claim
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1. A method of sensitizing a cancer cell to glucocorticoid-induced apoptosis or cell death, wherein said cell is resistant to glucocorticoid-induced apoptosis or cell death and wherein the expression level of CASP1 gene and/or NLRP3 gene in said cell is increased as compared to a corresponding glucocorticoid-sensitive control, comprising contacting the cell with an effective amount of an inhibitor of CASP1.
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Abstract
The invention provides methods for overcoming glucocorticoid resistance of cancers by inhibition of CASP1. Also disclosed are diagnostic methods for determining glucocorticoid resistance potential by measuring expression level or promoter methylation status of CASP1 gene and/or NLRP3 gene.
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38 Claims
- 1. A method of sensitizing a cancer cell to glucocorticoid-induced apoptosis or cell death, wherein said cell is resistant to glucocorticoid-induced apoptosis or cell death and wherein the expression level of CASP1 gene and/or NLRP3 gene in said cell is increased as compared to a corresponding glucocorticoid-sensitive control, comprising contacting the cell with an effective amount of an inhibitor of CASP1.
- 2. A method of killing a cancer cell, wherein said cell is resistant to glucocorticoid-induced apoptosis or cell death and wherein the expression level of CASP1 gene and/or NLRP3 gene in said cell is increased as compared to a corresponding glucocorticoid-sensitive control, comprising contacting the cell with an amount of an inhibitor of CASP1 that is effective to sensitize the cell to glucocorticoid-induced apoptosis or cell death and further comprising contacting the cell with an effective amount of a glucocorticoid.
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9. A method of treating a glucocorticoid-resistant cancer in a subject in need thereof, wherein the expression level of CASP1 gene and/or NLRP3 gene in cancer cells of the subject is increased as compared to a corresponding glucocorticoid-sensitive control, which method comprises:
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a) (i) determining the expression level of CASP1 gene and/or NLRP3 gene in cancer cells from the subject or (ii) determining the methylation level of CASP1 gene promoter and/or NLRP3 gene promoter in cancer cells from the subject, and b) administering to the subject (i) a therapeutically effective amount of an inhibitor of CASP1 and (ii) a therapeutically effective amount of a glucocorticoid. - View Dependent Claims (10, 15, 18, 25, 26, 27, 28, 29)
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- 16. A method of treating a glucocorticoid-resistant cancer in a subject in need thereof, wherein the expression level of CASP1 gene and/or NLRP3 gene in cancer cells of the subject is increased as compared to a corresponding glucocorticoid-sensitive control, which method comprises administering to the subject (i) a therapeutically effective amount of an inhibitor of CASP1 and (ii) a therapeutically effective amount of a glucocorticoid.
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