Treatment of cancer

Abstract

This disclosure provides agents, compositions and methods of treating cancer by inhibiting histone lysine specific demethylase 1 (LSD1) and/or and a histone lysine specific demethylase 2 (LSD2). Agents and compositions comprise statins and/or inhibitors of LSD1/2.

1 . A method for treating cancer in a subject comprising administering to a subject in need thereof a therapeutically effective amount of an epigenetic modulating adjuvant agent in conjunction with at least one chemotherapy, wherein the epigenetic modulating adjuvant agent promotes chemo-protection and reducing chemo-resistance. 
     
     
         2 . A method for treating chemotherapy resistant cancer in a subject, the method comprising:
 a. determining whether chemotherapy resistant cancer cell population of the subject are susceptible to an epigenetic modulating agent; and if so   b. administering to the subject a therapeutically effective amount of the epigenetic modulating agents, wherein the agent treats chemotherapy resistant cancer in the subject by inducing apoptosis of the chemotherapy resistant cancer cells, and wherein the apoptosis induced is at least 10% compared to cancer cells of the subject in the absence of the epigenetic modulating agent.   
     
     
         3 . The method of  claim 2 , wherein the susceptibility to an epigenetic modulating agent is determined comprising:
 i. providing a population of cancer cells derived from a subject;   ii. contacting the cells with at least one epigenetic modulating adjuvant agent; and   iii. measuring the methylation on H3K4Me2-containing DNA sequences, wherein an increase in methylation on H3K4Me2-containing DNA sequences indicate that the cancer cell population is susceptible to the at least one epigenetic modulating adjuvant agent.   
     
     
         4 . A method for enhancing the drug efficacy of at least one cancer chemotherapy in a subject comprising administering to the subject in need thereof a therapeutically effective amount of at least one an epigenetic modulating adjuvant agent in conjunction with the at least one chemotherapy to promote chemo-protection and reducing the development of chemo-resistance cancer cells in the subject. 
     
     
         5 . A method for assessing the susceptible of a cancer cell population to at least one epigenetic modulating adjuvant agent comprising providing a population of cancer cells derived from a subject, contacting the cells with at least one epigenetic modulating adjuvant agent, and measuring the methylation on H3K4Me2-containing DNA sequences, wherein an increase in methylation on H3K4Me2-containing DNA sequences indicate that the cancer cell population is susceptible to the at least one epigenetic modulating adjuvant agent. 
     
     
         6 . The methods of  claim 1 , wherein the epigenetic modulating adjuvant agent is an inhibitor of a histone demethylase. 
     
     
         7 . The methods of  claim 6 , wherein the histone demethylase is histone lysine specific demethylase 1 (LSD1) and/or and a histone lysine specific demethylase 2 (LSD2). 
     
     
         8 . The methods of  claim 7 , wherein the inhibitor is a statin. 
     
     
         9 . The methods of  claim 1 , wherein the at least one chemotherapy is an alkylating chemotherapeutic drug. 
     
     
         10 . A method for treating cancer in a subject comprising administering to a subject in need thereof a therapeutically effective amount of an inhibitor of a histone lysine specific demethylase 1 (LSD1) and/or and a histone lysine specific demethylase 2 (LSD2). 
     
     
         11 . The method of  claim 10 , wherein cancer cells of the subject has been determined to be susceptible to apoptosis induced by the inhibitor of LSD1 and/or LSD2. 
     
     
         12 . The method of  claim 11 , wherein the apoptosis induced is at least 10% compared to cancer cells of the subject in the absence of the inhibitor of LSD1 and/or LSD2. 
     
     
         13 . The method of  claim 11 , wherein the susceptibility to apoptosis induced by the inhibitor of LSD1 and/or LSD2 is determined by:
 a. providing a population of cancer cells derived from a subject;   b. contacting the cells with at least one epigenetic modulating adjuvant agent; and   c. measuring the methylation on H3K4Me2-containing DNA sequences, wherein an increase in methylation on H3K4Me2-containing DNA sequences indicate that the cancer cell population is susceptible to the at least one epigenetic modulating adjuvant agent   
     
     
         14 . The method of  claim 10 , wherein the inhibitor of LSD1 and/or LSD2 is a statin. 
     
     
         15 . The method of  claim 14 , wherein the statin is selected from the group consisting of fluvastatin, lovastatin, simvastatin, mevastatin, pravastatin, atorvastatin, and rosuvastatin. 
     
     
         16 . The method of  claim 10 , wherein the inhibitor of LSD1 and/or LSD2 is a monoamine oxidase inhibitor. 
     
     
         17 . The method of  claim 16 , wherein the monoamine oxidase inhibitor is tranylcypromine, derivatives or analogues thereof. 
     
     
         18 . The method of  claim 10 , wherein the inhibitor of LSD1 and/or LSD2 is administered by a route selected from the group consisting of: intravenous, intramuscular, subcutaneous, intradermal, topical, intraperitoneal, intrathecal, intrapleural, intrauterine, rectal, vaginal, intrasynovial, intraocular/periocular, intratumor, and parenteral administration. 
     
     
         19 . The method of  claim 10 , wherein the inhibitor of LSD1 and/or LSD2 is administered in conjunction with at least one additional cancer therapy to achieve a combination cancer therapy. 
     
     
         20 . The method of  claim 19 , wherein the at least one additional cancer therapy is selected from the group consisting of radiation therapy, chemotherapy, immunotherapy and gene therapy.