Claims
- 1. A method of killing cancer cells comprising causing an accumulation of activated Bcr-Abl in the nucleus to induce apoptosis.
- 2. A method of killing cancer cells expressing Bcr-Abl comprising administration of a kinase inhibitor and a nuclear export inhibitor simultaneously, followed by administration of the nuclear export inhibitor alone.
- 3. A method of killing cancer cells expressing Bcr-Abl comprising administration of a kinase inhibitor and leptomycin B (LMB) simultaneously, followed by administration of LMB alone.
- 4. The method of claim 2, wherein the kinase inhibitor is selected from the group comprising STI571, PD173955 and PD180970.
- 5. A method of claim 2, wherein the cancer cells are leukemic cancer cells.
- 6. A method of killing cancer cells in a solid tumor comprising administration of a nucleic acid expression cassette encoding Bcr-Abl, allowing time for the expression of the gene product, followed by simultaneous administration of a kinase inhibitor and leptomycin B (LMB) simultaneously, followed by administration of LMB alone.
- 7. The method of claim 6, wherein the nucleic acid expression cassette is a viral vector, or DNA alone or coupled with a reagent to enhance delivery of the nucleic acid into the cell.
- 8. A method of killing cancer cells in a solid tumor comprising sequentially administering to the tumor a nucleic acid expression cassette encoding Bcr-Abl containing a defective nuclear export signal (NES), allowing time for gene expression, followed by simultaneous treatment with a kinase inhibitor and LMB.
- 9. The method of claim 8, wherein the nucleic acid expression cassette is a viral vector or DNA alone or coupled with a reagent to enhance delivery.
- 10. A method of killing cancer cells in a solid tumor comprising administering to the tumor a nucleic acid expression cassette encodes a Bcr-Abl that is constituitively nuclear.
- 11. The method of claim 10, wherein the constituitively nuclear Bcr-Abl contains a disrupted nuclear export signal and at least one heterologous nuclear localization signal.
- 12. The method of claim 10, wherein the nucleic acid expression cassette is a viral vector, or DNA alone or coupled with a reagent to enhance delivery.
- 13. A method for purging bone marrow of Bcr-Abl expressing cells comprising, removing bone marrow cells from the body, and treating cells concurrently with a kinase inhibitor and a nuclear export inhibitor followed by treatment with the nuclear export inhibitor alone.
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority of U.S. provisional application Ser. No. 60/215,595 filed Jun. 30, 2000 which is incorporated herein by reference in its entirety.
GOVERNMENT INTEREST
[0002] The invention was made with government support from the National Institutes of Health under grant numbers CA 43054 and HL57900.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US01/20602 |
6/29/2001 |
WO |
|