COMPOSITIONS AND METHODS FOR TREATING WITH A COMBINATION OF ALTERNATING ELECTRIC FIELDS AND DNA-DEPENDENT PROTEIN KINASE INHIBITORS
Disclosed herein is the use of alternating electric fields and a DNA-dependent PK inhibitor to treat cancer. Disclosed herein is the use of alternating electric fields and a DNA-dependent PK inhibitor for inducing cell death. Disclosed herein is the use of alternating electric fields and a DNA-dependent PK inhibitor for inhibiting DNA repair in a cancer cell having double stranded DNA breaks. Disclosed herein is the use of alternating electric fields and a DNA-dependent PK inhibitor for increasing efficacy of radiation therapy.
1 . A method of treating a subject having cancer comprising:
a) applying an alternating electric field to a target site of the subject for a period of time, wherein the target site comprises one or more cancer cells, and
b) administering a therapeutically effective amount of a DNA-dependent protein kinase (PK) inhibitor to the subject.
2 . The method of claim 1 , wherein the cancer is ovarian cancer, hepatobiliary cancer, prostate cancer, pancreatic cancer, head and neck cancers, glioblastoma, gliosarcoma, leukemia, or non-small cell lung cancer.
3 . The method of claim 1 , wherein the subject having cancer has undergone or is currently undergoing radiation therapy or chemotherapy.
4 . The method of claim 1 , wherein the one or more cancer cells at the target site have double stranded DNA breaks.
5 . The method of claim 1 , wherein at least one DNA repair mechanism in the one or more cancer cells at the target site is inhibited.
6 . The method of claim 5 , wherein the DNA repair mechanism inhibited is homologous recombination repair, non-homologous end joining repair, or both.
7 . The method of claim 1 , wherein one or more cancer cells at the target site undergo cell death.
8 . The method of claim 1 , wherein the therapeutically effective amount of a DNA-dependent protein kinase (PK) inhibitor is administered orally, subcutaneously or intravenously.
9 . A method of inducing cell death of a cancer cell comprising:
a) exposing the cancer cell to an alternating electric field for a period of time, and
b) exposing the cancer cell to a DNA-dependent PK inhibitor.
10 . The method of claim 9 , wherein the cancer cell is simultaneously exposed to radiation or was previously exposed to radiation.
11 . A method of inhibiting DNA repair in a cancer cell exposed to or previously exposed to radiation comprising:
c) exposing the cancer cell to an alternating electric field for a period of time, and
d) exposing the cancer cell to a DNA-dependent PK inhibitor.
12 . The method of claim 9 , wherein the cancer cell is in a subject.
13 . The method of claim 12 , wherein exposing the cancer cell to an alternating electric field comprises administering the alternating electric field to a target site of the subject, wherein the target site comprises one or more cancer cells.
14 . The method of claim 9 , wherein the cancer cell is from ovarian cancer, hepatobiliary cancer, prostate cancer, pancreatic cancer, head and neck cancers, glioblastoma, gliosarcoma, leukemia, or non-small cell lung cancer.
15 . The method of claim 9 , wherein the DNA-dependent PK inhibitor is Nedisertib, VX-984, CC-115, CC-122, AZD7648, matinib, vemurafenib, gefitinib, Peposertib (M3814), MSC2490484A, LY294002, JU-57788, CC-115, BAY-8400, SF2523, LTURM34, Compound 401, AMA-37, IC 86621, DNA-PK-IN-1/2/3/4/5/6/7/8/9, NU7026 or NU 7441 or a combination thereof.
16 . The method of claim 15 , wherein the therapeutically effective amount of VX-984 is 50-720 mg/day.
17 . The method of claim 9 , wherein at least one DNA repair mechanism of the cancer cells is inhibited.
18 . The method of claim 9 , wherein the cancer cells undergo cell death.
19 . The method of claim 1 , wherein the alternating electric field has a frequency and field strength, wherein the frequency is between 100 KHz and 1 MHz.