Treating tumors using TTFields combined with a PARP inhibitor
Tumor-Treating Fields elicit a conditional vulnerability to PARP inhibitors (e.g., Olaparib) in certain cancer cells such as non-small cell lung cancer (NSCLC) cell lines. This conditional vulnerability is exploited in a method of killing cancer cells that comprises delivering a PARP inhibitor to the cancer cells and applying an alternating 80-300 kHz electric field to the cancer cells. At least a portion of the applying step is performed simultaneously with at least a portion of the delivering step. In some embodiments, an additional step of treating the cancer cells with a radiation therapy is added to the method. In some embodiments, the frequency of the alternating electric field is between 100 and 200 kHz.
1. A method of killing lung cancer cells, the method comprising:
delivering a PARP inhibitor to the lung cancer cells; and
applying an alternating electric field to the lung cancer cells, the alternating electric field having a frequency between 80 and 300 kHz, wherein at least a portion of the applying step is performed simultaneously with at least a portion of the delivering step.
2. The method of claim 1 , wherein the PARP inhibitor comprises Olaparib.
3. The method of claim 1 , wherein the lung cancer cells are non-small cell lung cancer (NSCLC) cells.
4. The method of claim 1 , wherein the applying step has a duration of at least 72 hours.
5. The method of claim 1 , wherein the frequency of the alternating electric field is between 100 and 200 kHz.
6. The method of claim 1 , wherein the alternating electric field has a field strength of at least 1 V/cm in at least some of the lung cancer cells.
7. The method of claim 6 , wherein the applying step has a duration of at least 72 hours and wherein the frequency of the alternating electric field is between 100 and 200 kHz.
8. The method of claim 7 , wherein the PARP inhibitor comprises Olaparib.
9. The method of claim 8 , wherein the lung cancer cells are NSCLC cells.
10. The method of claim 1 , wherein the concentration of the PARP inhibitor is from about 10 to about 50 μM.
11. The method of claim 10 , wherein the PARP inhibitor is Olaparib.
12. A method of killing lung cancer cells, the method comprising:
delivering a PARP inhibitor to the lung cancer cells;
applying an alternating electric field to the lung cancer cells, the alternating electric field having a frequency between 80 and 300 kHz, wherein at least a portion of the applying step is performed simultaneously with at least a portion of the delivering step; and
treating the lung cancer cells with a radiation therapy.
13. The method of claim 12 , wherein the PARP inhibitor comprises Olaparib.
14. The method of claim 12 , wherein the lung cancer cells are NSCLC cells.
15. The method of claim 12 , wherein the alternating electric field has a field strength of at least 1 V/cm in at least some of the lung cancer cells.
16. The method of claim 15 , further comprising repeating the delivering, applying, and treating steps at least five times.
17. The method of claim 16 , wherein each repetition of the treating step comprises delivering at least 2 Gy of radiation to a target area.
18. The method of claim 16 , wherein each repetition of the treating step comprises delivering at least 4 Gy of radiation to a target area.
19. The method of claim 16 , wherein the frequency of the alternating electric field is between 100 and 200 kHz.
20. The method of claim 16 , wherein the treating step is performed immediately after the applying step in each repetition.
21. The method of claim 16 , wherein the applying step is performed immediately after the treating step in each repetition.
22. The method of claim 12 , wherein the concentration of the PARP inhibitor is from about 10 to about 50 μM.
23. The method of claim 22 , wherein the PARP inhibitor is Olaparib.