Methods and assays for combination treatment of cancer

Abstract

The technology described herein is directed to the treatment of cancer, e.g. methods and assays relating to selecting and administering a chemotherapy with or without an EZH2 inhibitor.

What is claimed herein is: 
     
         1 . A method of treating cancer, the method comprising:
 administering or prescribing a topoisomerase I inhibitor and an EZH2 inhibitor to a subject determined to have a sensitizing mutation of BRG1, EGFR, or B-RAF in a tumor cell.   
     
     
         2 . The method of  claim 1 , wherein the EZH2 inhibitor is selected from the group consisting of:
 an inhibitory nucleic acid; DZNep; and S-adenosyl-L-homocysteine.   
     
     
         3 . The method of  claim 1 , wherein the topoisomerase I inhibitor is selected from the group consisting of:
 camptothecins; topotecan; irinotecan; indenoisoquinolines; indotecan; and   indimitecan; and lamellarin D.   
     
     
         4 . The method of  claim 1 , wherein the sensitizing mutation of BRG1 comprises a mutation selected from the group consisting of:
 a mutation which inactivates the ATPase activity of BRG1; a mutation which decreases the expression of BRG1; P270*; Q729*; W764R; T58*; and M272* wherein the * denotes truncation.   
     
     
         5 . The method of  claim 1 , wherein the sensitizing mutation of EGFR comprises a mutation selected from the group consisting of:
 a mutation which increased the expression level of EGFR; E746_A750del; E746_A749del; T790M; and L858R.   
     
     
         6 . The method of  claim 1 , wherein the sensitizing mutation of B-RAF comprises a mutation selected from the group consisting of:
 G496A and L597V.   
     
     
         7 . The method of  claim 1 , wherein the presence of the mutation is determined using an assay selected from the group consisting of:
 hybridization; sequencing; exome capture; PCR; and high-throughput sequencing.   
     
     
         8 . The method of  claim 1 , wherein the mutation is present in the genomic DNA or in the mRNA transcripts of the tumor cell. 
     
     
         9 . The method of  claim 1 , wherein the cancer is selected from the group consisting of:
 lung cancer; non-small cell lung cancer; ovarian cancer; EGFR-expressing ovarian cancer; B-Raf V600E melanomas; breast cancer; colon cancer; EGFR-mutated cancers; EGFR-mutated breast cancers; and EGFR-mutated colon cancers.   
     
     
         10 . The method of  claim 1 , further comprising the step of generating a report based on the detection of a sensitizing mutation in BRG1, EGFR, or B-RAF by a non-human machine. 
     
     
         11 . A method of treating cancer, the method comprising:
 administering or prescribing a EGFR inhibitor and an EZH2 inhibitor to a subject determined to have a sensitizing mutation of BRG1, EGFR, or B-RAF in a tumor cell.   
     
     
         12 . The method of  claim 11 , wherein the EZH2 inhibitor is selected from the group consisting of:
 an inhibitory nucleic acid; DZNep; and S-adenosyl-L-homocysteine.   
     
     
         13 . The method of  claim 11 , wherein the EGFR inhibitor is selected from the group consisting of:
 erlotinib; gefitinib; lapatinib; afatinib; CI-1033; neratinib; CP-724714; TAK-285; AST-1306; ARRY334543; Arry-380; AG-1478; dacomitinib; desmethyl erlotinib; OSI-420; AZD8931; AEE788; pelitinib; CUDC-101; WS8040; WZ4002; WZ3146; AG-490; XL647; PD153035 HC1; BMS-599626; AG 825; AG 494; AG 555; BIBU 1361; BIBX 1382; DAPH; JNJ 28871063; lavendustin A; and hypericin.   
     
     
         14 . The method of  claim 11 , wherein the sensitizing mutation of BRG1 comprises a mutation selected from the group consisting of:
 a mutation which inactivates the ATPase activity of BRG1; a mutation which decreases the expression of BRG1; P270*; Q729*; W764R; T58*; and M272* wherein the * denotes truncation.   
     
     
         15 . The method of  claim 11 , wherein the sensitizing mutation of EGFR comprises a mutation selected from the group consisting of:
 a mutation which increased the expression level of EGFR; E746_A750del; E746_A749del; T790M; and L858R.   
     
     
         16 . The method of  claim 11 , wherein the sensitizing mutation of B-RAF comprises a mutation selected from the group consisting of:
 G496A and L597V.   
     
     
         17 . The method of  claim 11 , wherein the presence of the mutation is determined using an assay selected from the group consisting of:
 hybridization; sequencing; exome capture; PCR; and high-throughput sequencing.   
     
     
         18 . The method of  claim 11 , wherein the mutation is present in the genomic DNA or mRNA transcripts of the tumor cell. 
     
     
         19 . The method of  claim 11 , wherein the cancer is selected from the group consisting of:
 lung cancer; non-small cell lung cancer; ovarian cancer; EGFR-expressing ovarian cancer; B-Raf V600E melanomas; breast cancer; colon cancer; EGFR-mutated cancers; EGFR-mutated breast cancers; and EGFR-mutated colon cancers.   
     
     
         20 . The method of  claim 11 , further comprising the step of generating a report based on the detection of a sensitizing mutation in BRG1, EGFR, or B-RAF by a non-human machine.