Methods for restoring sensitivity to TTFields in TTFields-resistant cancer cells with PTGER3 inhibitors

Patent metadata

Field	Value
Publication number	US-11911610-B2
Application number	US-202016832572-A
Country	US
Kind code	B2
Filing date	Mar 27, 2020
Priority date	Mar 29, 2019
Publication date	Feb 27, 2024
Grant date	Feb 27, 2024

Abstract

Methods of reducing the viability of cancer cells, preventing cancer cells of a subject from developing resistance to TTFields, and restoring sensitivity of cancer cells to TTFields by recommending or prescribing a PTGER3 inhibitor to a subject and applying an alternating electric field to the cancer cells are provided. In some instances, sensitivity of cancer cells to TTFields can be restored with one or more PTGER3 inhibitors (e.g., NSAIDs, cox2 inhibitors).

First claim

What is claimed is:

1. A method of reducing viability of TTFields-resistant cancer cells in a subject, the method comprising:
administering a Prostaglandin E Receptor 3 (PTGER3) inhibitor to the subject, wherein the PTGER3 inhibitor is selected from the group consisting of one or more of aspirin, ibuprofen, L798,106, and DG041; and
applying an alternating electric field to the cancer cells of the subject, the alternating electric field having a frequency between 100 and 500 kHz,
wherein the cancer cells are glioblastoma cells.

2. The method of claim 1 , wherein the alternating electric field has a frequency between 100 and 300 kHz.

3. The method of claim 1 , wherein the PTGER3 inhibitor is L798,106, or DG041.

4. The method of claim 1 , wherein the PTGER3 inhibitor is aspirin or ibuprofen.

5. The method of claim 1 , the PTGER3 inhibitor is administered to the subject at a concentration of from about 1 to 500 nanomolar for L798,106, or 0.1 to 2 millimolar for aspirin, or 0.5 to 50 nanomolar for DG041.

6. The method of claim 5 , wherein the concentration of the PTGER3 inhibitor in the subject is maintained for at least about 3 days to 5 weeks.

Assignees

• Novocure Gmbh

Inventors

• Tran David
• Le Son Bang
• Chen Dongjiang

Classifications

• A61K31/192

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• A61N1/205 Primary

  for promoting a biological process · CPC title

• A61K31/415

  1,2-Diazoles · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/41 Primary

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title