# US 12,005,253 B2 · Compositions and methods for increasing cancer cell sensitivity to alternating electric fields > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,005,253 B2 - Document ID: US12005253B2 - Status: Granted - Kind: B2 - Application number: 17/841,968 - Filed: 2022-06-16 - Published: 2023-01-05 - Granted: 2024-06-11 - Earliest claimed: 2021-06-30 - Assignees: Novocure GmbH - Applicants: Novocure GMBH - Inventors: Lilach Avigdor; Tali Voloshin-Sela - Web page: https://patentgrep.com/patent/US12005253B2 ## CPC - A61K 31/416: condensed with carbocyclic ring systems, e.g. indazole - A61N 1/36002: {Cancer treatment, e.g. tumour} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61N 1/0476: {Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) ## Abstract Disclosed herein are methods of increasing sensitivity of a cancer cell to alternating electric fields comprising exposing the cancer cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength, and exposing the cancer cell to an IGFR1 inhibitor, JNK inhibitor, RPS6 inhibitor or ERK inhibitor. Disclosed are methods of increasing treatment efficacy comprising applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells, and administering a therapeutically effective amount of one or more of an IGF1R inhibitor, JNK inhibitor, RPS6 inhibitor, and/or ERK inhibitor to the subject. Disclosed are methods of treating a subject having cancer comprising applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells, and administering a therapeutically effective amount of one or more of an IGF1R inhibitor, JNK inhibitor, RPS6 inhibitor, and/or ERK inhibitor to the subject. Disclosed are methods of reducing viability of cancer cells using an alternating electric field for a period of time, the alternating electric field having a frequency and field strength in combination with either an IGF1R inhibitor, JNK inhibitor, RPS6 inhibitor, and/or ERK inhibitor. Disclosed are methods of increasing apoptosis of a cancer cell comprising exposing the cancer cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength; and exposing the cancer cell to an IGFR1 inhibitor, JNK inhibitor, RPS6 inhibitor or ERK inhibitor. ## Claims ### Claim 1 A method of increasing sensitivity of a cancer cell to alternating electric fields comprising: a. exposing the cancer cell to an alternating electric field for a period of time, the alternating electric field having a frequency and field strength, and b. exposing the cancer cell to an IGFR1 inhibitor or JNK inhibitor. ### Claim 2 (depends on 1) The method of claim 1, wherein the frequency of the alternating electric field is between 100 and 500 kHz. ### Claim 3 (depends on 2) The method of claim 2, wherein the frequency of the alternating electric field is between 180 and 220 kHz. ### Claim 4 (depends on 1) The method of claim 1, wherein the cancer cell is a glioblastoma cell, ovarian cell, or lung metastatic carcinoma cell. ### Claim 5 (depends on 1) The method of claim 1, wherein the cancer cell is in a subject. ### Claim 6 (depends on 1) The method of claim 1, wherein the cancer cells are exposed to the alternating electric field and IGFR1 inhibitor, JNK inhibitor, RPS6 inhibitor or ERK inhibitor simultaneously. ### Claim 7 (depends on 1) The method of claim 1, wherein the IGFR1 inhibitor is selected from one or more of the group consisting of: cixutumumab (IMC-Al2), Figitumumab (CP-751, 871), Dalotuzumab (MK-0646; h7C10), Ganitumab (AMG 479), R1507, SCH 717454 (19D12), AVE1642 (EM164), BIIB022, MEDI-573, Linsitinib (OSI-096), BMS-754807, BVP 51004, XL228, INSM-18 (NDGA), NVP-AEW541, GSK1904529A, NVP-ADW742, BMS-536924, Ceritinib (LDK378), AG-1024, GSK1838705A, SBI-477, PQ 401, AZD3463, NT157, Brigatinib (AP26113), Picropodophyllin (PPP), and 5961. ### Claim 8 (depends on 1) The method of claim 1, wherein the JNK inhibitor is selected from one or more of the group consisting of: SP600125, AS601245, N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides, azaquinolone analog168 and N-alkyl (propyl and butyl)-bearing pyrazoloanthrone scaffolds, 7-(6-N-phenylaminohexyl)amino-2H-anthra[1,9-cd]pyrazol-6-one, HCC or Bi-78D3, PYC98, PYC71N, adamantyl azaquinolone, Pyrimidinyl-substituted benzazole-acetonitriles, 6-anilinoindazoles, 20-anilino-4,40-bipyridines, isoxazole derivatives, XG-102, 4-quinolone analog 13c, 4-phenylisoquinolone 11g, ginsenoside Rg1, and pyridopyrimidinone derivatives, JNK-IN-1 to JNK-IN-12, IRAK1, PIK3C3, PIP4K2C, PIP5K3, anthrapyrazolone, indazoles, aminopyrazoles, aminopyridines, pyridine carboxamides, benzothien-2-ylamides and benzothiazol-2-yl acetonitriles, quinoline derivatives, and aminopyrimidines. ### Claim 9 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, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells, and (b) administering a therapeutically effective amount of an IGFR1 inhibitor or JNK inhibitor to the subject. ### Claim 10 A method of reducing viability of a cancer cell in a subject comprising: (a) applying an alternating electric field to a target site of the subject for a period of time, the alternating electric field having a frequency and field strength, wherein the target site comprises one or more cancer cells, and (b) administering a therapeutically effective amount of an IGFR1 inhibitor or JNK inhibitor to the subject. ### Claim 11 The method of 9, wherein the cancer is glioblastoma, ovarian, or lung metastatic carcinoma. ### Claim 12 (depends on 9) The method of claim 9, wherein the IGFR1 inhibitor is selected from one or more of the group consisting of: cixutumumab (IMC-Al2), Figitumumab (CP-751, 871), Dalotuzumab (MK-0646; h7C10), Ganitumab (AMG 479), R1507, SCH 717454 (19D12), AVE1642 (EM164), BIIB022, MEDI-573, Linsitinib (OSI-096), BMS-754807, BVP 51004, XL228, INSM-18 (NDGA), NVP-AEW541, GSK1904529A, NVP-ADW742, BMS-536924, Ceritinib (LDK378), AG-1024, GSK1838705A, SBI-477, PQ 401, AZD3463, NT157, Brigatinib (AP26113), Picropodophyllin (PPP), 5961. ### Claim 13 (depends on 9) The method of claim 9, wherein the JNK inhibitor is selected from one or more of the group consisting of: SP600125, AS601245, N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides, azaquinolone analog168 and N-alkyl (propyl and butyl)-bearing pyrazoloanthrone scaffolds, 7-(6-N-phenylaminohexyl)amino-2H-anthra[1,9-cd]pyrazol-6-one, HCC or Bi-78D3, PYC98, PYC71N, adamantyl azaquinolone, Pyrimidinyl-substituted benzazole-acetonitriles, 6-anilinoindazoles, 20-anilino-4,40-bipyridines, isoxazole derivatives, XG-102, 4-quinolone analog 13c, 4-phenylisoquinolone 11g, ginsenoside Rg1, and pyridopyrimidinone derivatives, JNK-IN-1 to JNK-IN-12, IRAK1, PIK3C3, PIP4K2C, PIP5K3, anthrapyrazolone, indazoles, aminopyrazoles, aminopyridines, pyridine carboxamides, benzothien-2-ylamides and benzothiazol-2-yl acetonitriles, quinoline derivatives, and aminopyrimidines. ### Claim 14 (depends on 1) The method of claim 1, wherein the frequency is between 100 and 500 kHz. ### Claim 15 (depends on 14) The method of claim 14, wherein the frequency is between 180 and 220 kHz.