Methods of Normalizing Aberrant Glycolytic Metabolism in Cancer Cells
Viability of cancer cells (e.g., glioblastoma cells) can be reduced by administering mannose to the cancer cells; and applying an alternating electric field with a frequency between 100 and 500 kHz to the cancer cells. Susceptibility to treatment with an alternating electric field can be determined by measuring uptake of a PKM2 probe (e.g., [18F]DASA) before and after treatment with an alternating electric field. Notably, experiments show that the combination of mannose and the alternating electric field produces a synergistic anti-glioblastoma result.
1 . A method of determining susceptibility of patient to treatment of cancer with alternating electric fields comprising:
administering a PKM2 probe to a patient having cancer;
measuring a first level of PKM2 uptake in cancer cells of the patient;
exposing the cancer cells to treatment using alternating electric fields at a frequency between 100 and 500 kHz after measuring the first level;
measuring a second level of PKM2 uptake in the cancer cells; and
determining if the patient is susceptible to treatment using alternating electric fields based on whether the first level is higher than the second level by at least 5%.
2 . The method of claim 1 , wherein the PKM2 probe comprises [18F]DASA-23 having the following structure:
3 . The method of claim 1 , wherein the alternating electric fields have a frequency between 180 and 220 kHz.
4 . The method of claim 1 , wherein the cancer is glioblastoma.
5 . A method of reducing a viability of cancer cells, comprising:
administering a PKM2 probe to a patient having cancer;
measuring a first level of PKM2 expression or uptake of the PKM2 probe in cancer cells from the patient;
exposing the cancer cells to alternating electric fields at a frequency between 100 and 500 kHz for a first interval of time after measuring the first level;
measuring a second level of PKM2 expression or uptake of the PKM2 probe in the cancer cells after the first interval of time; and
continuing exposing the cancer cells to alternating electric fields if the first level is higher than the second level by at least 5%.
6 . The method of claim 5 , wherein the PKM2 probe comprises [18F]DASA-23 having the following structure:
7 . The method of claim 5 , wherein the alternating electric fields have a frequency between 180 and 220 kHz.
8 . The method of claim 5 , wherein the cancer cells are glioblastoma cells.
9 . A method of determining susceptibility of patient to treatment of cancer using alternating electric fields, comprising:
administering mannose labelled with an imaging probe to cells of patient having cancer;
measuring a first level of uptake of the mannose labelled with an imaging probe in cancer cells from the patient;
treating the cancer cells with alternating electric fields at a frequency between 100 and 500 kHz for a first interval of time after measuring the first level;
measuring a second level of uptake of the mannose labelled with an imaging probe in the cancer cells after the first interval of time; and
continuing treatment of the cancer cells using alternating electric fields if the first level is lower than the second level by at least 10%.
10 . The method of claim 9 , wherein the alternating electric fields have a frequency between 180 and 220 kHz.
11 . The method of claim 9 , wherein the cancer is glioblastoma.
12 . A method of reducing a viability of cancer cells, comprising administering mannose to cancer cells of a patient having cancer and then exposing the cancer cells to alternating electric fields at a frequency between 100 and 500 kHz.
13 . The method of claim 12 , wherein the alternating electric fields have a frequency between 180 and 220 kHz.
14 . The method of claim 12 , wherein the cancer cells are glioblastoma cells.
15 . A method of reducing a viability of cancer cells, comprising:
administering a PKM2 probe to a patient having cancer;
measuring a first level of PKM2 expression or uptake of the PKM2 probe in cancer cells from the patient;
exposing the cancer cells to alternating electric fields at a frequency between 100 and 500 kHz for a first interval of time after measuring the first level;
measuring a second level of PKM2 expression or uptake of the PKM2 probe in the cancer cells after the first interval of time; and
administering a chemotherapeutic agent to the cancer cells if the first level is higher than the second level by at least 5%.
16 . The method of claim 15 , wherein the chemotherapeutic agent is selected from the group consisting of tamoxifen, cisplatin, 5-fluorouracil (5-FU), and docetaxel.
17 . The method of claim 16 , wherein the chemotherapeutic agent is cisplatin.
18 . The method of claim 15 , further comprising continuing exposing the cancer cells to alternating electric fields.
19 . The method of claim 15 , wherein the cancer cells are glioblastoma cells.