Novel isoform of anaplastic lymphoma kinase and its uses

Abstract

The present invention relates to a Truncated isoform of Anaplastic Lymphoma Kinase (“TALK”). Expression of this isoform is associated with malignancy and with responsiveness to ALK inhibitors. Detection of the isoform may be used in diagnostic and therapeutic methods. Because it arises as a result of variant transcription rather than genetic rearrangement, its presence would be undetected by genomic testing.

1 .- 18 . (canceled) 
     
     
         19 . A method of determining whether an anti-cancer effect is likely to be produced in a cancer by an ALK inhibitor, comprising determining whether one or more cell of the cancer contains a detectable TALK, wherein the presence of a detectable TALK in the cell indicates that an ALK inhibitor would have an anti-cancer effect on the cancer. 
     
     
         20 . A method of treating a subject having a cancer comprising: (a) determining whether a subject is likely to obtain therapeutic benefit from an ALK inhibitor, comprising determining whether one or more cancer cell of the subject contains a detectable TALK, wherein the presence of a detectable TALK in the cancer cell of the subject indicates that the subject is likely to benefit from an ALK inhibitor; and (b) treating the subject who is likely to benefit from an ALK inhibitor with a therapeutic amount of an ALK inhibitor. 
     
     
         21 . The method of  claim 20 , comprising treating the subject with an alternative therapy other than an ALK inhibitor if no detectable TALK is present in the cancer cell of the subject. 
     
     
         22 . The method of  claim 20 , wherein the cancer is selected from the group consisting of melanoma, thyroid carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, renal clear cell carcinoma, and breast cancer. 
     
     
         23 . The method of  claim 20 , wherein the ALK inhibitor is selected from the group consisting of crizotinib, ceritinib, NVP-TAE684, alectinib; AP26113, ASP-3026, CEP-37440, NMS-E628, PF-06463922, TSR-011, RXDX-101, and X-396. 
     
     
         24 . A kit for determining whether an anti-cancer effect is likely to be produced in a cancer by an ALK inhibitor, comprising a means for determining the presence of a detectable TALK in one or more cell of the cancer. 
     
     
         25 . The kit of  claim 24 , comprising means for determining the level of a TALK mRNA transcript, a TALK cDNA molecule corresponding thereto, and/or a TALK polypeptide encoded thereby in one or more cell of the cancer. 
     
     
         26 . The kit of  claim 25 , wherein the means for determining the level of a TALK mRNA transcript is selected from the group consisting of probe hybridization, polymerase chain reaction (PCR), Northern blot, sequencing, microarray, and combinations thereof. 
     
     
         27 . The kit of  claim 25 , wherein the means for determining the level of a TALK cDNA molecule is PCR. 
     
     
         28 . The kit of  claim 25 , wherein the means for determining the level of a TALK polypeptide is selected from the group consisting of antibody binding, immunohistochemistry, Western blot, a functional assay, enzyme linked immunosorbent assay (ELISA), radioimmunoassays (RIA), enzyme immunoassays (EIA), mass spectrometry, 1-D or 2-D gel-based analysis system, immunoprecipitation, and combinations thereof.