Use of melanoma inhibitory activity (mia) protein as an early indicator for therapeutic response in melanoma

Abstract

The present invention provides a method for determining a response of a mammalian subject having melanoma tumor cells to treatment with a melanoma inhibitory agent. In one aspect, the method comprises (a) determining a first concentration of melanoma inhibitory activity protein (MIA) in a first biological sample taken from the mammalian subject before treatment with the melanoma inhibitory agent; (b) determining a second concentration of MIA in a second biological sample from the mammalian subject taken after treatment with the melanoma, inhibitory agent; and (c) comparing the first and second concentrations of MIA, wherein a decrease in the second concentration of MIA measured in the second biological sample as compared to the first concentration of MIA measured in the first biological sample indicates a positive response to the treatment with the melanoma inhibitory agent.

1 . A method for treating a mammalian subject having melanoma tumor cells with a melanoma inhibitory agent, comprising:
 (a) determining a first concentration of melanoma inhibitory activity protein (MIA) in a first biological sample taken from a mammalian subject prior to initiation of treatment with the melanoma inhibitory agent;   (b) initiating the treatment by administering the melanoma inhibitory agent to the mammalian subject;   (c) determining a second concentration of MIA in a second biological sample from the mammalian subject taken after administration of the melanoma inhibitory agent; and   (d) comparing the first and second concentrations of MIA, wherein a decrease in the second concentration of MIA measured in the second biological sample as compared to the first concentration of MIA measured in the first biological sample indicates the effectiveness of the method.   
     
     
         2 . The method of  claim 1 , wherein the melanoma inhibitory agent is a small molecule selected from the group consisting of CHIR-265, sorafenib and CHIR-258. 
     
     
         3 . The method of  claim 1 , wherein a decrease in the second concentration of MIA in the second biological sample measured within 3 months after initiation of treatment indicates the effectiveness of the method. 
     
     
         4 . The method of  claim 1 , wherein a decrease in the second concentration of MIA in the second biological sample measured within one week after treatment indicates the effectiveness of the method. 
     
     
         5 . The method of  claim 1 , wherein a decrease of at least 20% in the second concentration of MIA in the second biological sample as compared to the first concentration of MIA in the first biological sample correlates with tumor growth inhibition in the mammalian subject. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the biological sample is a blood sample. 
     
     
         8 . The method of  claim 1 , wherein the concentration of MIA in the biological sample is determined using an antibody that specifically binds to MIA. 
     
     
         9 .- 15 . (canceled) 
     
     
         16 . A method of treating a melanoma patient with a melanoma inhibitory agent, comprising
 (a) determining a first concentration of melanoma inhibitory activity protein (MIA) in a first biological sample taken from the patient prior to initiation of treatment with the melanoma inhibitory agent;   (b) initiating the treatment by administering the melanoma inhibitory agent to the patient;   (c) determining a second concentration of MIA in a second biological sample from the mammalian subject taken after initiation of treatment with the melanoma inhibitory agent;   (d) comparing said first and second concentrations of MIA; and   (e) continuing administering the melanoma inhibitory agent to the patient if the second concentration of MIA is reduced by at least 20% in comparison to the first concentration of MIA.   
     
     
         17 . The method of  claim 16 , wherein the melanoma inhibitory agent is a small molecule selected from the group consisting of CHIR-265, sorafenib and CHIR-258. 
     
     
         18 .- 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the first biological sample and the second biological sample comprise human melanoma tumor cells. 
     
     
         21 . The method of  claim 1 , wherein the treatment is initiated if the first concentration of MIA is at least 16 ng/mL. 
     
     
         22 . The method of  claim 1 , wherein the concentration of MIA in the biological sample is determined using immunofluorescence staining, flow cytometry, mass spectrometry, immunocytochemistry, immunohistochemistry, immunoblotting, ELISA or Western blot. 
     
     
         23 . The method of  claim 1 , wherein the melanoma inhibitory agent is CHIR-265. 
     
     
         24 . The method of  claim 16 , wherein the first biological sample and the second biological sample comprise human melanoma tumor cells. 
     
     
         25 . The method of  claim 16 , wherein the biological sample is a blood sample. 
     
     
         26 . The method of  claim 16 , wherein the treatment is initiated if the first concentration of MIA is at least 16 ng/mL. 
     
     
         27 . The method of  claim 16 , wherein the concentration of MIA in the biological sample is determined using immunofluorescence staining, flow cytometry, mass spectrometry, immunocytochemistry, immunohistochemistry, immunoblotting, ELISA or Western blot. 
     
     
         28 . The method of  claim 16 , wherein the concentration of MIA in the biological sample is determined using an antibody that specifically binds to MIA. 
     
     
         29 . The method of  claim 16 , wherein the melanoma inhibitory agent is CHIR-265.