Methods of detecting a polypeptide having anaplastic lymphoma kinase activity in kidney cancer

Abstract

The invention provides methods to identify, diagnose, and treat kidney cancer through the detection of expression and/or activity of anaplastic lymphoma kinase (ALK). The detection of the presence of a polypeptide with ALK kinase activity (e.g., by detecting expression and/or activity of the polypeptide), identify those kidney cancers that are likely to respond to an ALK-inhibiting therapeutic.

1 .- 30 . (canceled) 
     
     
         31 . A method for treating a human patient with kidney cancer or suspected kidney cancer driven by an ALK fusion polypeptide with ALK kinase activity, said method comprising the step of administering a composition comprising a therapeutically effective amount of an ALK-inhibiting therapeutic to the patient. 
     
     
         32 .- 34 . (canceled) 
     
     
         35 . A method for treating a human patient having kidney cancer or suspected kidney cancer comprising the steps of:
 (a) detecting the presence or activity of an ALK fusion polypeptide with ALK kinase activity in a biological sample of the kidney cancer or suspected kidney cancer of the patient; and   (b) administering a therapeutically effective amount of a composition comprising an ALK-inhibiting therapeutic to the mammalian patient.   
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 31 , wherein the ALK-inhibiting therapeutic is selected from the group consisting of PF-02341066, NVT TAE-684, and AP26113. 
     
     
         38 . The method of  claim 31 , wherein the ALK-inhibiting therapeutic is selected from the group consisting of CEP-14083, CEP-14513, CEP11988, WHI-P131 and WHI-P154. 
     
     
         39 . The method of  claim 35 , wherein the ALK-inhibiting therapeutic is selected from the group consisting of PF-02341066, NVT TAE-684, and AP26113. 
     
     
         40 . The method of  claim 35 , wherein the ALK-inhibiting therapeutic is selected from the group consisting of CEP-14083, CEP-14513, CEP11988, WHI-P131 and WHI-P154. 
     
     
         41 . A method for treating a human subject having kidney cancer that expresses a human Anaplastic Lymphoma Kinase (ALK) fusion polypeptide, comprising
 administering to the human subject a small molecule that a) binds to the ATP-binding cleft and b) directly inhibits the kinase activity of the ALK fusion polypeptide, in an amount effective to treat the kidney cancer,   wherein the −ALK fusion polypeptide comprises the ALK kinase domain as set forth in SEQ ID NO: 3.   
     
     
         42 . The method of  claim 39 , wherein the ALK fusion polypeptide also comprises the intracytoplasmic domain of ALK as set forth in SEQ ID NO: 4. 
     
     
         43 . The method of  claim 41 , wherein the ALK fusion polypeptide is an Echinoderm Microtubule-Associated Protein-Like 4 (EML4)-ALK fusion polypeptide. 
     
     
         44 . The method of  claim 41 , wherein said kidney cancer is a granular cell cancer or a squamous cell cancer. 
     
     
         45 . The method of  claim 43 , wherein said kidney cancer is a granular cell cancer or a squamous cell cancer.