Methods of treating cancer using lsd1 inhibitors in combination with immunotherapy

Abstract

Provided herein are methods of treating cancer using LSD1 inhibitors in combination with immunotherapy.

1 . A method of treating cancer in a patient, the method comprising:
 administering to a patient in need thereof a therapeutically effective amount of a lysine-specific demethylase 1A (LSD1) inhibitor, to thereby treat cancer in the patient.   
     
     
         2 . A method of treating cancer in a patient, the method comprising:
 administering to a patient in need thereof a therapeutically effective amount of a lysine-specific demethylase 1A (LSD1) inhibitor and at least one immunotherapy, to thereby treat cancer in the patient.   
     
     
         3 - 6 . (canceled) 
     
     
         7 . The method of  claim 2 , wherein the at least one immunotherapy is selected from the group consisting of: an antibody, an adoptive cellular therapy, an antibody-drug conjugate, a toxin, a cytokine therapy, a cancer vaccine, and a checkpoint inhibitor wherein the checkpoint inhibitor is a CTLA-4 inhibitor, an OX40 inhibitor, a TIM3 inhibitor, or a LAG3 inhibitor. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the LSD1 inhibitor is selected from the group consisting of: a small molecule, an antibody, and an inhibitory nucleic acid. 
     
     
         10 . The method of  claim 9 , wherein the LSD1 inhibitor is an inhibitory nucleic acid, and wherein the inhibitory nucleic acid is a small interfering RNA or a short hairpin RNA. 
     
     
         11 . The method of  claim 10 , wherein the inhibitory nucleic acid is a short hairpin RNA and the short hairpin RNA comprises SEQ ID NO: 2. 
     
     
         12 . The method of  claim 9 , wherein the LSD1 inhibitor is a small molecule selected from the group consisting of: tranylcypromine, RN 1 dihydrochloride, GSK-LSD1, GSK2879552, ORY1001, GSK690, namoline, Cpd 2d, S2101, OG-L002, SP2509, CBB2007 and IMG-7289. 
     
     
         13 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the cancer is a primary tumor. 
     
     
         22 . The method of  claim 1 , wherein the cancer is a metastatic tumor. 
     
     
         23 . The method of  claim 1 , wherein the cancer is selected from the group consisting of: melanoma, acute myeloid leukemia (AML), squamous cell carcinoma, renal cell carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), gastric cancer, bladder cancer, kidney cancer, head and neck cancer, Ewing sarcoma, Hodgkin's lymphoma, Merkel cell carcinoma, breast cancer and prostate cancer. 
     
     
         24 . The method of  claim 1 , wherein the cancer is a non-T-cell-infiltrating cancer. 
     
     
         25 . The method of  claim 1 , wherein the cancer is a PD-1 and/or PD-L1 refractory cancer. 
     
     
         26 . The method of  claim 1 , wherein the cancer is a PD-1 and/or PD-L1 resistant cancer. 
     
     
         27 . The method of  claim 1 , wherein the patient has previously received a cancer treatment. 
     
     
         28 . The method of  claim 1 , wherein administering occurs at least once a week. 
     
     
         29 . The method of  claim 1 , wherein administering is via intravenous, subcutaneous, intraperitoneal, rectal, and/or oral administration. 
     
     
         30 - 32 . (canceled) 
     
     
         33 . The method of  claim 1 , wherein the method further comprises administering a chemotherapeutic agent to the patient. 
     
     
         34 . The method of  claim 1 , wherein treating comprises reducing the volume of primary tumor in the patient. 
     
     
         35 . The method of  claim 1 , wherein treating comprises delaying cancer progression in the patient. 
     
     
         36 . The method of  claim 1 , wherein treating comprises modifying the tumor microenvironment of a cancer in the patient, sensitizing cancer to a checkpoint inhibitor therapy, decreasing the risk of developing at least one metastatic tumor in the patient, decreasing the rate of tumor growth in the patient, and/or eliciting tumor-intrinsic double-stranded RNA stress in a cancer cell in the patient. 
     
     
         37 - 40 . (canceled) 
     
     
         41 . The method of  claim 1 , wherein the method comprises identifying the patient as being resistant to PD-1 inhibitor or PD-L1 inhibitor treatment. 
     
     
         42 . The method of  claim 2 , wherein the method comprises identifying the patient as being resistant to PD-1 inhibitor or PD-L1 inhibitor treatment.