Inhibition of thymine DNA glycosylase in the treatment of cancer
The invention provides compositions, kits, and methods for inducing growth arrest, differentiation, or senescence of cancer cells that express thymine DNA glycosylase, and treating the cancer accordingly. The methods comprise inhibiting expression or biologic activity of thymine DNA glycosylase in cancer cells. Inhibition of thymine DNA glycosylase in cancer cells may induce the cells to revert to a healthy, non-cancerous phenotype and/or may induce the cells to senesce. Cancer cells include melanoma, lung, prostate, pancreatic, ovarian, brain, colon, recto-sigmoid colon, and breast cancer cells.
1. A method of treating a patient having melanoma, prostate cancer, colon cancer, or glioblastoma, comprising administering to the blood of the patient in need thereof an amount of aurothioglucose effective to inhibit TDG in cells of the melanoma, prostate cancer, colon cancer, or glioblastoma.
2. The method according to claim 1 , further comprising administering temozolomide to the patient.
3. The method according to claim 1 , further comprising administering cisplatin to the patient.
4. The method according to claim 1 , further comprising administering vincristine to the patient.
5. The method according to claim 1 , further comprising administering a RAD51 inhibitor to the patient.
6. A method of treating a patient having prostate cancer comprising administering to the blood of the patient in need thereof an inhibitor of TDG in the amount effective to inhibit TDG in cells of prostate cancer, wherein the TDG inhibitor comprises aurothioglucose.
7. The method according to claim 6 , further comprising administering temozolomide to the patient.
8. The method according to claim 6 , further comprising administering cisplatin to the patient.
9. The method according to claim 6 , further comprising administering vincristine to the patient.
10. The method according to claim 6 , further comprising administering a RAD51 inhibitor to the patient.
11. The method according to claim 1 , wherein the patient has melanoma.
12. The method according to claim 1 , wherein the patient has glioblastoma.
13. A method of treating a patient having colon cancer comprising administering to the blood of the patient in need thereof an inhibitor of TDG in the amount effective to inhibit TDG in cells of the colon cancer, wherein the TDG inhibitor comprises aurothioglucose.
14. The method according to claim 13 , further comprising administering temozolomide to the patient.
15. The method according to claim 13 , further comprising administering cisplatin to the patient.
16. The method according to claim 13 , further comprising administering vincristine to the patient.
17. The method according to claim 13 , further comprising administering a RAD51 inhibitor to the patient.