Methods for the treatment, diagnosis, and prognosis of cancer
First Claim
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1. A method for treating cancer comprising administering to a subject in need thereof an effective amount of a pharmaceutical comprising an active agent or compound which inhibits antizyme inhibitor, and a pharmaceutically acceptable carrier or diluent.
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Abstract
We have discovered that antizyme inhibitor (AZI) is expressed at increased levels in highly proliferating cells. We have also discovered that inhibiting antizyme inhibitor, including inhibiting its expression, reduces the growth of cancer cells. The present invention is directed to the use of inhibitors of antizyme inhibitor for the treatment of cancer, the use of antizyme inhibitor for the diagnosis and prognosis of cancer, and methods for identifying novel cancer treatments.
76 Citations
21 Claims
- 1. A method for treating cancer comprising administering to a subject in need thereof an effective amount of a pharmaceutical comprising an active agent or compound which inhibits antizyme inhibitor, and a pharmaceutically acceptable carrier or diluent.
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3. The method of claim 3, wherein the cancer is selected from the group consisting of stomach cancer, lung cancer, liver cancer, brain cancer, and adrenal cancer.
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5. The method of claim 5, wherein the RNA interfering agent is a double-stranded, short interfering RNA (siRNA).
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6. The method of claim 6, wherein said siRNA inhibits antizyme inhibitors by transcriptional silencing expression of the antizyme inhibitors.
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8. A method for screening for a compound or agent useful for the treatment of cancer, comprising:
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a) providing a cell comprising a reporter plasmid comprising a nucleic acid sequence encoding antizyme inhibitor;
b) contacting said cell with a test compound or agent;
c) comparing the level of reporter expression in the presence of the test compound with the level of reporter expression in a control sample in the absence of the test compound; and
d) determining whether or not the test compound increases or decreases the level of reporter expression, wherein a decrease in the level of reporter expression indicates the compound or agent is an antizyme inhibitor.
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9. A method for screening for a compound or agent useful for the treatment of cancer, comprising:
- screening a library of candidate compounds to identify those compounds which inhibit antizyme inhibitor.
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10. A method of diagnosing cancer in a patient, comprising:
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a) determining the level of antizyme inhibitor in the test sample; and
b) comparing the level of antizyme inhibitor or its variants in the test sample with the level of antizyme inhibitor present in a normal control sample;
wherein a higher level of antizyme inhibitor in the test sample as compared to the level in the normal control sample is indicative of cancer. - View Dependent Claims (11, 12, 13, 14, 15, 16, 18, 19)
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17. The method of 16, wherein the antizyme inhibitor protein level is measured by Immunoblotting or ELISA.
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20. A method for prognostic evaluation of a patient suspected of having or having cancer comprising:
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a) determining the level of antizyme inhibitor in a test sample obtained from a patient;
b) comparing the level determined in step (a) to a range of antizyme inhibitor known to be present in a biological sample obtained from a normal patient that does not have cancer; and
c) determining the prognosis of said patient based on the comparison of step (b), wherein a high level of antizyme inhibitor in step (a) indicates an aggressive form of cancer and therefore a poor prognosis.
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21. A kit for measuring antizyme inhibitor levels comprising separate vials containing antibodies, or antibody fragments, which selectively bind human antizyme inhibitor.
Specification