Combination therapy for cancer
AssigneeThe Regents of the University of California
InventorsMichael Karin, Hua Su
Life of this patent
Estimating the term…
Abstract
Provided herein are methods and compositions for treating cancer through a combination of an inhibitor of macropinocytosis upregulation and an autophagy inhibitor. Also provided are methods and compositions for inducing cell death of cancer cells, and transgenic animal models regarding same.
Claims35
A method of inducing cell death of a cancer cell, the method comprising, contacting the cancer cell with:
- (1) an inhibitor of macropinocytosis upregulation, wherein the inhibitor of macropinocytosis upregulation is selected from 5-(N-ethyl-N-isopropyl) amiloride (EIPA), 3-methylsulphonyl-4-piperidinobenzoyl)guanidine methanesulphonate (HOE-694), amiloride and amiloride derivatives, eganelisib, IPI-549, MBO-167, wortmannin, LP1-106, XRK3F2, ML385, Brusatol, LY294002, a sodium-proton exchanger inhibitor, a sodium-calcium exchanger inhibitor, a sodium channel inhibitor, an inhibitor of activity or expression of one or more proteins selected from NRF2, PIK3CG, PAK1, SLC9A1, SNX5, SDC1, NHE1, p110α, p110γ, p62, CDC42, EGFR, EGF, or a combination thereof;
- and
- (2) an autophagy inhibitor, wherein the autophagy inhibitor is selected from 3-Methyladenine (3-MA), LY294002, Bafilomycin A1 (Baf A1), Chloroquine (CO), hydroxychloroquine (HCO), ABT-737, an IKKα downregulator, obatoclax, Clarithromycin, Resveratrol, Quinacrine, 4-Acetylantroquinonol B, antroquinonol, Epigallocatechin gallate (EGCG), MRT68921 dihydrochloride, ULK1 inhibitors, MRT67307, SBI-0206965, ULK-100, ULK-101, DCC-3116, SAR405, Vps34-IN1 (PIK-III), SU1261, Vps34 inhibitors, or a combination thereof,
- thereby inducing cell death of the cancer cell.
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A method of treating cancer in a subject in need thereof, the method comprising administering to the subject;
- (a) an inhibitor of macropinocytosis upregulation, wherein the inhibitor of macropinocytosis upregulation is selected from 5-(N-ethyl-N-isopropyl) amiloride (EIPA), 3-methylsulphonyl-4-piperidinobenzoyl)guanidine methanesulphonate (HOE-694), amiloride and amiloride derivatives, eganelisib, IPI-549, MBO-167, wortmannin, LP1-106, XRK3F2, ML385, Brusatol, LY294002, a sodium-proton exchanger inhibitor, a sodium-calcium exchanger inhibitor, a sodium channel inhibitor, an inhibitor of activity or expression of one or more proteins selected from NRF2, PIK3CG, PAK1, SLC9A1, SNX5, SDC1, NHE1, p110α, p110γ, p62, CDC42, EGFR, EGF, or a combination thereof;
- and
- (b) an autophagy inhibitor, wherein the autophagy inhibitor is selected from 3-Methyladenine (3-MA), LY294002, Bafilomycin A1 (Baf A1), Chloroquine (CQ), hydroxychloroquine (HCQ), ABT-737, obatoclax, Clarithromycin, Resveratrol, Quinacrine, 4-Acetylantroquinonol B, antroquinonol, Epigallocatechin gallate (EGCG), MRT68921 dihydrochloride, ULK1 inhibitors, an IKKα downregulator, MRT67307, SBI-0206965, ULK-100, ULK-101, DCC-3116, SAR405, Vps34-IN1 (PIK-III), SU1261, Vps34 inhibitors, or a combination thereof,
- thereby treating cancer in the subject.
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A composition for inducing cancer cell death comprising an inhibitor of macropinocytosis upregulation and an autophagy inhibitor, wherein:
- (a) the inhibitor of macropinocytosis upregulation is selected from 5-(N-ethyl-N-isopropyl)amiloride (EIPA), 3-methylsulphonyl-4-piperidinobenzoyl)guanidine methanesulphonate (HOE-694), amiloride and amiloride derivatives, eganelisib, IPI-549, MBQ-167, wortmannin, LP1-106, XRK3F2, LY294002, an inhibitor of activity or expression of one or more proteins of NRF2, PIK3CG, PAK1, SLC9A1, SNX5, SDC1, NHE1, p110α, p110γ, p62, CDC42, EGFR, EGF, ML385, brusatol, or a combination thereof;
- and
- (b) the autophagy inhibitor is selected from the group consisting of 3-Methyladenine (3-MA), LY294002, bafilomycin A1 (Baf A1), chloroquine (CQ), hydroxychloroquine (HCQ), ABT-737, obatoclax, clarithromycin, resveratrol, ruinacrine, 4-acetylantroquinonol B, antroquinonol, epigallocatechin gallate (EGCG), MRT68921 dihydrochloride, ULK1 inhibitors, an IKKα downregulator, MRT67307, SBI-0206965, ULK-100, ULK-101, DCC-3116, SAR405, Vps34-IN1 (PIK-III), SU1261, Vps34 inhibitors, or a combination thereof.
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Dependencies are inferred from the claim text.