Resistance biomarkers for hdac inhibitors

Abstract

Provided herein are methods for identifying a cancer patient at risk for resistance to an HDAC inhibitor therapy, comprising obtaining a tumor sample from the cancer patient; detecting the presence of Testis-specific Y-encoded-like protein 5 (TSPYL5) expression in the sample; quantifying a level of the TSPYL5 expression in the sample, wherein a high level of the TSPYL5 expression, relative to a defined expression threshold of the TSPYL5, correlates with resistance to the HDAC inhibitor therapy; and applying the correlation to identify the cancer patient at risk for resistance to the HDAC inhibitor therapy. Also provided is a method for identifying a cancer patient with an increased likelihood of a positive clinical response to an HDAC inhibitor therapy comprising obtaining a tumor sample from the cancer patient; detecting the presence of Testis-specific Y-encoded-like protein 5 (TSPYL5) expression in said sample; quantifying a level of said TSPYL5 expression in said sample, wherein a low level of the TSPYL5 expression, relative to a defined expression threshold of the TSPYL5, identifies said cancer patient with an increased likelihood of a positive clinical response to said HDAC inhibitor therapy. Related methods and compositions are also provided.

1 - 19 . (canceled) 
     
     
         20 . A method of treating cancer comprising initiating romidepsin therapy to a cancer patient, wherein said cancer patient has an expression level of Testis-Specific Y-encoded-like protein 5 (TSPYL5) lower than a defined TSPYL5 expression level threshold. 
     
     
         21 . The method of  claim 20 , wherein the level of the TSPYL5 expression is determined by measuring the amount of TSPYL5 protein using an immunoassay. 
     
     
         22 . The method of  claim 21 , wherein the immunoassay is an immune-polymerase chain reaction (immuno-PCR). 
     
     
         23 . The method of  claim 20 , wherein romidepsin is administered intravenously. 
     
     
         24 . The method of  claim 23 , wherein the dose of romidepsin is a range of between 0.5 and 28 mg/m 2 . 
     
     
         25 . The method of  claim 24 , wherein the dose of romidepsin is a range of between 8 and 14 mg/m 2 . 
     
     
         26 . The method of  claim 25 , wherein the dose of romidepsin is about 8 mg/m 2 . 
     
     
         27 . The method of  claim 25 , wherein the dose of romidepsin is about 10 mg/m 2 . 
     
     
         28 . The method of  claim 25 , wherein the dose of romidepsin is about 12 mg/m 2 . 
     
     
         29 . The method of  claim 25 , wherein the dose of romidepsin is about 14 mg/m 2 . 
     
     
         30 . The method of  claim 25 , wherein romidespin is administered in the dose of about 14 mg/m 2  an as IV infusion over a 4 hour period on days 1, 8, and 15 of the 28 day cycle. 
     
     
         31 . The method of  claim 20 , wherein romidepsin is administered orally. 
     
     
         32 . The method of  claim 31 , wherein the dose of romidepsin is a range of between 10 and 300 mg/m 2 . 
     
     
         33 . The method of  claim 32 , wherein the dose of romidepsin is a range of between 25 and 75 mg/m 2 . 
     
     
         34 . The method of  claim 33 , wherein the dose of romidepsin is about 25 mg/m 2 . 
     
     
         35 . The method of  claim 33 , wherein the dose of romidepsin is about 50 mg/m 2 . 
     
     
         36 . The method of  claim 33 , wherein the dose of romidepsin is about 75 mg/m 2 . 
     
     
         37 . The method of  claim 33 , wherein romidespin is administered in the dose of about 50 mg/m 2  on days 1, 8, and 15 of the 28 day cycle. 
     
     
         38 . The method of  claim 20 , wherein the cancer is leukemia or lymphoma. 
     
     
         39 . The method of  claim 20 , wherein the cancer is a solid tumor selected from the group consisting of lung, breast, colon, liver, pancreas, renal, prostate, ovarian and brain cancer.