Claims
- 1. A method of diagnosing a tamoxifen-resistant breast or prostate tumor in an individual comprising:
providing a biological sample from the individual, and detecting p38 MAPK activity or expression within said sample, wherein higher p38 MAPK activity or expression in said biological sample compared to a sample obtained from a control tumor known to be tamoxifen-sensitive indicates that said biological sample is more tamoxifen resistant than the control tumor.
- 2. The method of claim 1 wherein the biological sample is derived from a tissue biopsy.
- 3. The method of claim 1 wherein the biological sample is obtained from a tumor.
- 4. The method of claim 1 wherein said detecting comprises detecting p38 MAPK activity.
- 5. The method of claim 4 wherein p38 MAPK activity is detected by a phosphorylation assay selected from the group consisting of an in-gel kinase assay, an immunohistochemical assay, an immunofluorescence assay, a Western blot assay, and an ELISA.
- 6. The method of claim 1 wherein said detecting comprises detecting p38 MAPK expression.
- 7. The method of claim 6 wherein p38 MAPK expression is detected by nucleic acid hybridization.
- 8. The method of claim 6 wherein p38 MAPK expression is detected using an expression assay selected from the group consisting of a PCR assay, a Northern blotting assay, an in situ hybridization assay, a nuclear run-on assay, a reporter gene assay, an immunohistochemical assay, an immunofluorescence assay, a Western blot assay, and an ELISA.
- 9. A method of diagnosing an estrogen withdrawal-resistant breast or prostate tumor in an individual comprising:
providing a biological sample from the individual, and detecting p38 MAPK activity or expression within said sample, wherein higher p38 MAPK activity or expression in said biological sample compared to a sample obtained from a control tumor known to be estrogen withdrawal-sensitive indicates that said biological sample is more estrogen withdrawal-resistant that the control tumor.
- 10. The method of claim 9 wherein the biological sample is derived from a tissue biopsy.
- 11. The method of claim 9 wherein the biological sample is obtained from a tumor.
- 12. The method of claim 9 wherein said detecting comprises detecting p38 MAPK activity.
- 13. The method of claim 12 wherein p38 MAPK activity is detected by a phosphorylation assay selected from the group consisting of an in-gel kinase assay, an immunohistochemical assay, an immunofluorescence assay, a Western blot assay, and an ELISA.
- 14. The method of claim 9 wherein said detecting comprises detecting p38 MAPK expression.
- 15. The method of claim 14 wherein p38 MAPK expression is detected by nucleic acid hybridization.
- 16. The method of claim 14 wherein p38 MAPK expression is detected using an expression assay selected from the group consisting of a PCR assay, a Northern blotting assay, an in situ hybridization assay, a nuclear run-on assay, a reporter gene assay, an immunohistochemical assay, an immunofluorescence assay, a Western blot assay, and an ELISA.
- 17. A method of identifying a molecule that prevents or reverses acquired tamoxifen resistance in a breast or prostate tumor comprising:
contacting a tamoxifen-resistant tumor cell with a test molecule; and detecting p38 MAPK activity or expression within said sample; wherein lower p38 MAPK activity or expression in said tumor cell upon or after contact with the test molecule compared to the p38 MAPK activity or expression before contact with the test molecule indicates that the agent is likely to prevent or reverse acquired tamoxifen resistance in a tumor.
- 18. The method of claim 17 wherein said tumor cell is a breast tumor cell.
- 19. The method of claim 17 wherein said tumor cell is transfected with a nucleic acid comprising a p38 MAPK expression control sequence operably linked to a reporter gene.
- 20. A method of identifying a molecule that prevents or reverses acquired estrogen withdrawal resistance in a breast or prostate tumor comprising:
contacting an estrogen withdrawal-resistant tumor cell with a test molecule; and detecting p38 MAPK activity or expression within said sample; wherein lower p38 MAPK activity or expression in said tumor cell upon or after contact with the test molecule compared to the p38 MAPK activity or expression before contact with the test molecule indicates that the agent is likely to prevent or reverse acquired estrogen withdrawal resistance in the tumor.
- 21. The method of claim 20 wherein said tumor cell is a breast tumor cell.
- 22. The method of claim 20 wherein said tumor cell is transfected with a nucleic acid comprising a p38 MAPK expression control sequence operably linked to a reporter gene.
- 23. A method of reversing or preventing tamoxifen resistance in a tumor comprising:
contacting said tumor with a p38 MAPK inhibitor in an amount effective to inhibit p38 MAPK.
- 24. The method of claim 23 wherein said tumor is a breast tumor.
- 25. The method of claim 23 wherein said tumor is a human tumor.
- 26. The method of claim 23 wherein said tamoxifen resistance is acquired tamoxifen resistance.
- 27. The method of claim 23 wherein said p38 MAPK inhibitor is selected from the group consisting of antisense p38 MAPK nucleic acids and fragments thereof and anti-p38 MAPK antibodies and fragments thereof.
- 28. The method of claim 23 wherein said p38 MAPK inhibitor is selected from the group consisting of EO-1428, PD169316, SB202190, SB203580, SB239063, SB281832, VX-702, VX-745, ZM336372, RPR 200765A, and N-(3-tert-butyl-1-methyl-5-pyrazolyl)-N′-(4-(4-pyridinylmethyl)phenyl)urea.
- 29. A method of reducing, reversing or preventing endocrine resistance in a tumor comprising:
contacting said tumor with a p38 MAPK inhibitor in an amount effective to inhibit p38 MAPK.
- 30. The method of claim 29 wherein said tumor is a breast tumor.
- 31. The method of claim 29 wherein said said tumor is a human tumor.
- 32. The method of claim 29 wherein said endocrine resistance is de novo endocrine resistance.
- 33. The method of claim 29 wherein said endocrine resistance is acquired endocrine resistance.
- 34. The method of claim 29 wherein said endocrine resistance is tamoxifen resistance.
- 35. The method of claim 29 wherein said endocrine resistance is estrogen withdrawal resistance.
- 36. The method of claim 29 wherein said p38 MAPK inhibitor is selected from the group consisting of antisense p38 MAPK nucleic acids and fragments thereof and anti-p38 MAPK antibodies and fragments thereof.
- 37. The method of claim 29 wherein said p38 MAPK inhibitor is selected from the group consisting of EO-1428, PD169316, SB202190, SB203580, SB239063, SB281832, VX-702, VX-745, ZM336372, RPR 200765A, and N-(3-tert-butyl-1-methyl-5-pyrazolyl)-N′-(4-(4-pyridinylmethyl)phenyl)urea.
- 38. A method of increasing the tamoxifen sensitivity of tamoxifen-resistant tumor comprising:
contacting said tumor with a p38 MAPK inhibitor in an amount effective to inhibit p38 MAPK.
- 39. The method of claim 38 further comprising contacting said tumor with tamoxifen.
- 40. The method of claim 38 wherein said p38 MAPK inhibitor is selected from the group consisting of antisense p38 MAPK nucleic acids and fragments thereof and anti-p38 MAPK antibodies and fragments thereof.
- 41. The method of claim 38 wherein said p38 MAPK inhibitor is selected from the group consisting of EO-1428, PD169316, SB202190, SB203580, SB239063, SB281832, VX-702, VX-745, ZM336372, RPR 200765A, and N-(3-tert-butyl-1-methyl-5-pyrazolyl)-N′-(4-(4-pyridinylmethyl)phenyl)urea.
Government Interests
[0001] This application claims the benefit of U.S. Provisional Application Serial No. 60/299,824 filed on Jun. 21, 2001.
Provisional Applications (1)
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Number |
Date |
Country |
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60299824 |
Jun 2001 |
US |