COMPOSITIONS AND METHODS OF A CONCOMITANT THERAPY OF ALTERNATING ELECTRIC FIELDS AND N-CADHERIN INHIBITOR
Disclosed are methods of treating a subject in need thereof comprising applying an alternating electric field, at a frequency for a period of time, to a target site of the subject in need thereof; and administering a neural-cadherin (N-cadherin) inhibitor to the subject in need thereof. Disclosed are methods of preventing metastasis comprising applying an alternating electric field, at a frequency for a period of time, to a population of cells comprising one or more cancer cells; and contacting a N-cadherin inhibitor to the population of cells.
1 . A method of treating a subject in need thereof comprising:
a) applying an alternating electric field, at a frequency for a period of time, to a target site of the subject in need thereof; and
b) administering a neural-cadherin (N-cadherin) inhibitor to the subject in need thereof.
2 . The method of claim 1 , wherein the N-cadherin inhibitor is a calcium chelator or a N-cadherin antagonist.
3 . The method of claim 2 , wherein the calcium chelator is EGTA, Edetic acid, Citric acid, Edetate disodium anhydrous, or Edetate calcium disodium anhydrous.
4 . The method of claim 2 , wherein the N-cadherin antagonist is LCRF-0006, ADH-1, HAV-containing peptide, Trp-containing peptide, Compound 15, HAV dimeric, HAV-biomaterial, N-cadherin antibody, H-SWTLYTPSGQSK-NH2.
5 . The method of claim 4 , wherein the N-cadherin antibody is GC4, 2A9, or 1H7.
6 . The method of claim 1 , wherein the subject has cancer.
7 . The method of claim 6 , wherein the cancer is ovarian cancer or non-small cell lung cancer.
8 . The method of claim 1 , wherein the N-cadherin inhibitor reduces AKT phosphorylation, reduces PI3K/p85 recruitment to N-cadherin, or reduces metastasis in the subject.
9 . A method of reducing AKT phosphorylation or inhibiting the recruitment of the p85 subunit of PI3K to an N-cadherin complex in response to alternating electric fields comprising:
a) applying an alternating electric field, at a frequency for a period of time, to a population of cells comprising one or more fibroblasts; and
b) contacting a calcium chelator to the population of cells.
10 . A method of preventing metastasis in a subject having cancer comprising:
a) applying an alternating electric field, at a frequency for a period of time, to a population of cells comprising one or more cancer cells; and
b) contacting a N-cadherin inhibitor to the population of cells.
11 . The method of claim 10 , wherein the N-cadherin inhibitor is a calcium chelator or an N-cadherin antagonist.
12 . The method of claim 1 , wherein the alternating electric field is applied before, after, or simultaneously with administering the N-cadherin inhibitor to the subject.
13 . The method of claim 1 , wherein the frequency of the alternating electric field is between 50 kHz and 1 MHz.
14 . The method of claim 1 , wherein the frequency of the alternating electric field is about 150 or 250 kHz.
15 . The method of claim 1 , wherein the alternating electric field has a field strength of between 0.5 and 10 V/cm RMS.
16 . The method of claim 1 , further comprising administering a cancer therapeutic.
17 . The method of claim 1 , wherein after step a) and prior to step b) detecting an increase in N-cadherin expression in the subject.
18 . The method of claim 1 , wherein step b) is performed 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days after step a) is performed.
19 . The method of claim 1 , wherein the target site comprises cancer cells.
20 . The method of claim 19 , wherein the cancer cells are ovarian cancer cells or non-small cell lung cancer cells.