Biomarkers associated with brm inhibition

Abstract

The invention provides methods of detecting cancer biomarkers, such as one or more SWI/SNF complex mutations, in order to determine a cancer subject's amenability to therapeutic treatment with a BRM inhibitor. Kits, methods of screening for candidate FIRM inhibitors, and associated methods of treatment are also provided.

1 . A method of determining if a subject afflicted with a cancer associated with a BRG1 mutation will respond to therapeutic treatment with a BRM inhibitor, comprising:
 a) contacting a sample obtained from said subject with a reagent capable of detecting human cancer cells harboring one or more BRG1 mutations; and   b) comparing the sample obtained from said afflicted subject with a similar sample taken from a non-cancerous or normal control subject, wherein the presence of one or more BRG1 mutations in said sample obtained from said afflicted subject indicates said afflicted subject will respond to therapeutic treatment with a BRM inhibitor.   
     
     
         2 . The method of  claim 1 , wherein the cancer is squamous cell lung carcinoma, non-small cell lung carcinoma, large cell lung carcinoma, lung adenocarcinoma, liver or ovarian cancer. 
     
     
         3 . The method of  claim 1 , wherein the reagent capable of detecting human cancer cells harboring one or more BRG1 mutations or loss of BRG1 expression is an anti-BRG1 antibody. 
     
     
         4 . The method of  claim 1 , wherein the reagent capable of detecting human cancer cells harboring one or more BRG1 mutations is one or more PCR probes specific for one of the BRG1 mutations listed in Table 1, Table 2, and experimentally described herein. 
     
     
         5 . The method of  claim 1 , wherein the BRM inhibitor is a short hairpin RNA (shRNA) or short inhibitory RNA (siRNAs). 
     
     
         6 . The method of  claim 1 , wherein the BRM inhibitor is an antibody drug conjugate. 
     
     
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         14 . A method of screening for BRM inhibitors, said method comprising:
 a) contacting a sample containing one or more cells harboring one or more BRG1 mutations of loss of BRG1 expression with a candidate BRM inhibitor;   b) measuring the reduction in viability of said cells in said sample;   c) contacting a similar sample containing one or more cells harboring one or more BRG1 mutations or a loss of BRG1 expression with a known BRM inhibitor;   d) measuring the reduction in viability of said cells in said similar sample;   e) comparing the reduction in viability of said cells harboring one or more BRG1 mutations or loss of BRG1 expression from said sample with viability of said similar sample, wherein a similar reduction in viability indicates said candidate sample is a BRM inhibitor.   
     
     
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         22 . A method of determining if a subject afflicted with a cancer associated with BRG1 lack of expression or BRG1 protein loss of function will respond to therapeutic treatment with a BRM inhibitor, comprising:
 a) contacting a sample obtained from said subject with a reagent capable of detecting human cancer cells exhibiting BRG1 lack of expression; and   b) comparing the sample obtained from said afflicted subject with a similar sample taken from a non-cancerous or normal control subject, wherein the detection of BRG1 lack of expression in said sample obtained from said afflicted subject indicates said afflicted subject will respond to therapeutic treatment with a BRM inhibitor.