Methods of treating lung cancer by administration of an alk inhibitor

Abstract

Novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The invention also provides methods for determining the presence of these mutant polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides.

What is claimed is: 
     
         1 . A method for detecting the presence of a mutant Anaplastic Lymphoma Kinase (ALK) polypeptide in a circulating tumor cell, said method comprising the steps of:
 (a) obtaining a circulating tumor cell from a patient having cancer;   (b) utilizing at least one reagent that detects a mutant ALK polypeptide, to determine whether a mutant ALK polypeptide is present in said circulating tumor cell.   
     
     
         2 . The method of  claim 1 , wherein said at least one reagent is an antibody that binds to a mutant ALK polypeptide. 
     
     
         3 . The method of  claim 1 , wherein the detection in step (b) is implemented in an immunohistochemistry format. 
     
     
         4 . The method of  claim 1 , wherein the detection in step (b) is implemented in a flow cytometry format. 
     
     
         5 . The method of  claim 1 , wherein said cancer is lung cancer. 
     
     
         6 . The method of  claim 5 , wherein said lung cancer is non-small cell lung cancer (NSCLC).