Identification of Non-Small Cell Lung Carcinoma (NSCLC) Tumors Expressing PDGFR-ALPHA

Abstract

The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFRα) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFRα is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFRα-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFRα is expressed, and for determining whether a compound inhibits the progression of a PDGFRα-expressing mammalian NSCLC tumor.

What is claimed is: 
     
         1 . A method for identifying a mammalian non-small cell lung carcinoma (NSCLC) tumor that belongs to a subset of NSCLC tumors in which platelet-derived growth factor receptor alpha (PDGFRα) is expressed, said method comprising the step of determining whether PDGFRα is expressed in a biological sample comprising cells from a NSCLC tumor using at least one PDGFRα specific reagent, wherein expression of PDGFRα in said biological sample identifies said NSCLC tumor as belonging to a subset of NSCLC tumors in which PDGFRα is expressed. 
     
     
         2 . The method of  claim 1 , wherein said mammal is a human. 
     
     
         3 . The method of  claim 1 , wherein identifying said NSCLC tumor as belonging to a subset of NSCLC tumors in which PDGFRα is expressed Identifies said NSCLC tumor as being likely to respond to a composition comprising at least one PDGFRα-inhibiting therapeutic. 
     
     
         4 . The method of  claim 3 , wherein said PDGFRα-inhibiting therapeutic comprises a small molecule inhibitor of PDGFRα. 
     
     
         5 . The method of  claim 4 , wherein said small molecule inhibitor of PDGFRα is Imatinib mesylate (STI-571). 
     
     
         6 . The method of  claim 4  wherein said small molecule inhibitor of PDGFRα is an Imatinib mesylate (STI-571) analogue. 
     
     
         7 . The method of  claim 6 , wherein said Imatinib mesylate (STI-571) analogue is selected from the group consisting of BAY 43-93006, XL-999 and SU11248. 
     
     
         8 . The method of  claim 1 , wherein said biological sample comprises cells obtained from a tumor biopsy, a tumor fine needle aspirate, or a pleural effusion. 
     
     
         9 . The method of  claim 1 , wherein said PDGFRα-specific reagent comprises a PDGFRα-specific antibody. 
     
     
         10 . The method of  claim 9 , wherein said PDFGRα-specific antibody is a phosphorylation site-specific antibody. 
     
     
         11 . The method of  claim 1 , wherein said PDGFRα-specific reagent comprises a heavy-isotope labeled peptide (AQUA peptide) that corresponds to a PDGFRα peptide sequence. 
     
     
         12 . The method of  claim 11 , wherein said AQUA peptide is a peptide having a sequence selected from the group consisting of SEQ ID NOs: 3-8. 
     
     
         13 . The method of  claim 1 , wherein said method is implemented in a flow-cytometry (FC), immuno-histochemistry (IHC), or immuno-fluorescence (IF) assay format. 
     
     
         14 . A method for determining whether a compound inhibits the progression of a mammalian NSCLC tumor belonging to a subset of NSCLC tumors in which PDGFRα is expressed, said method comprising the step of determining whether said compound inhibits the expression and/or activity of PDGFRα in said NSCLC tumor. 
     
     
         15 . The method of  claim 14 , wherein inhibition of expression and/or activity of PDGFRα is determined by examining a biological sample comprising cells from said NSCLC tumor. 
     
     
         16 . The method of  claim 14 , wherein inhibition of expression and/or activity of PDGFRα is determined using at least one PDGFRα-specific reagent. 
     
     
         17 . The method of  claim 16 , wherein said PDGFRα-specific reagent comprises a phosphorylation-site specific antibody. 
     
     
         18 . A method for inhibiting the progression of a mammalian NSCLC tumor belonging to a subset of NSCLC tumors in which PDGFRα is expressed, said method comprising the step of inhibiting the expression and/or activity of PDGFRα in said tumor. 
     
     
         19 . The method of  claim 18 , wherein expression and/or activity of PDGFRα is inhibited with composition comprising Imatinib mesylate (STI-571) and/or an analogue of Imatinib mesylate (STI-571). 
     
     
         20 . The method of  claim 19 , wherein said analogue is selected from the group consisting of BAY 43-93006, XL-999 and SU11248.