Methods and Compositions for Treating Cancer
OwnerSteven R. Bartz, Peter Linsleyinventors
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Abstract
The present invention relates to methods and compositions for treating cancers by reducing the expression or activity of one or more of the genes encoding protein kinases ATR, MAST2, MAP3K6, TBK1, ADRBK2, CDKL2, LATS2, STK32B, STK11, DDR13 PSKH2, and NEK8, and/or the encoded kinases. The invention also relates to methods and compositions for determining the responsiveness of a cancer patient to anti-cancer drugs based on the status of one or more of such kinases. The invention further relates to methods and compositions for screening compounds that can be used to modulate the expression/activity of these kinases.
Claims71
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A method for treating a mammal having a cancer, comprising
- (a) administering to said mammal a therapeutically effective amount of a first agent, said first agent reducing the expression of a gene encoding a protein kinase selected from the group consisting of ATR, MAST2, MAP3K6, TBK1, ADRBK2, CDKL2, LATS2, STK32B, STK11, DDR1, PSKH2, and NEK8 and/or activity of said protein kinase;
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- (b) administering to said mammal a therapeutically effective amount of a composition comprising one or more anti-cancer agents.
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A method for evaluating sensitivity of a cell to the growth inhibitory effect of an anti-cancer agent, said method comprising determining a level of activity of a protein kinase selected from the group consisting of ATR, MAST2, MAP3K6, TBK1, ADRBK2, CDKL2, LATS2, STK32B, STK11, DDR1, PSKH2, and NEK8, and determining whether said level of activity is below a predetermined threshold level, wherein said activity level below the predetermined threshold level indicates that said cell is sensitive to the growth inhibitory effect of said anti-cancer agent.
A method for enhancing sensitivity of a cell to an anti-cancer agent, comprising contacting said cell with an agent that reduces the expression of a gene encoding a protein kinase selected from the group consisting of ATR, MAST2, MAP3K6, TBK1, ADRBK2, CDKL2, LATS2, STK32B, STK11, DDR1, PSKH2, and NEK8 and/or the activity of said protein kinase, said agent being in an amount sufficient to enhance sensitivity of said cell to an anti-cancer agent.
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A method of identifying a substance that is capable of enhancing sensitivity of a cell of a cell type to the growth inhibitory effect of an anti-cancer agent, wherein said substance is capable of reducing the expression of a first gene encoding a protein kinase selected from the group consisting of ATR, MAST2, MAP3K6, TBK1, ADRBK2, CDKL2, LATS2, STK32B, STK11, DDR1, PSKH2, and NEK8 and/or the activity of said protein kinase, said method comprising:
- (a) contacting a first cell of said cell type expressing said first gene with said anti-cancer agent in the presence of said candidate substance and measuring a first growth inhibitory effect;
- (b) contacting a second cell of said cell type expressing said first gene with said anti-cancer agent under the same conditions as (a) except in the absence of said candidate substance and measuring a second growth inhibitory effect;
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- (c) comparing said first and second growth inhibitory effects measured in said step (a) and (b),
- wherein a greater first growth inhibitory effect than said second growth inhibitory effect identifies said candidate substance as capable of enhancing sensitivity of a cell to the growth inhibitory effect of said anti-cancer agent.
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Dependencies are inferred from the claim text.