Anti-tnf induced apoptosis (atia) diagnostic markers and therapies

Abstract

The invention features diagnostic and therapeutic methods and compositions featuring Anti-TNF Induced Apoptosis (ATIA). AITA is useful as a diagnostic marker for cancer, in particular for glioblastoma. ATIA is also a therapeutic target in diseases such as cancer. The invention encompasses combination therapies where knockdown of ATIA is used in combination with other treatment. The invention also features kits for use in the diagnostic and therapeutic methods.

What is claimed is: 
     
         1 . A method of diagnosing a subject as having, or having a propensity to develop a neoplasia, the method comprising determining the level of expression or biological activity of an anti-TNF Induced Apoptosis (ATIA) polypeptide or nucleic acid in a subject sample wherein an alteration in the level of expression or biological activity relative to the expression or biological activity in a reference indicates that the subject has or has a propensity to develop a neoplasia. 
     
     
         2 . The method of  claim 1 , wherein the neoplasia is selected from the group consisting of: brain, pancreatic, and stomach neoplasia. 
     
     
         3 . A method of determining the progression of a brain neoplasia in a subject, the method comprising determining the expression or activity of an ATIA polypeptide or nucleic acid in a subject sample, wherein an alteration in the level of expression or activity relative to the level of expression in a reference indicates the progression of the a brain neoplasia in the subject. 
     
     
         4 . The method of  claim 1 , wherein the method is used to determine if a subject will be responsive to TRAIL therapy, chemotherapy, or radiation treatment. 
     
     
         5 . The method of  claim 1 , wherein the ATIA nucleic acid comprises a sequence selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, and SEQ ID: NO: 8, or fragments thereof. 
     
     
         6 . The method of  claim 1 , wherein the ATIA polypeptide comprises a sequence selected from the group consisting of: SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 9 and SEQ ID NO: 10, or fragments thereof. 
     
     
         7 . The method of  claim 1 , wherein the level of expression is determined in an immunological assay, enzyme-linked immunosorbent assay (ELISA), or immunohistochemical assay. 
     
     
         8 . The method of  claim 7 , wherein the ELISA is used to detect the extracellular portion of ATIA. 
     
     
         9 . The method of  claim 8 , wherein the extracellular portion comprises a sequence selected from the group consisting of: SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, or fragments thereof. 
     
     
         10 . The method of  claim 1 , wherein the alteration is an increase. 
     
     
         11 . The method of  claim 10 , wherein the increase corresponds to an increased sensitivity to TRAIL-induced cell death. 
     
     
         12 . A polypeptide comprising an isolated ATIA protein, or fragment thereof, wherein the protein is upregulated in a neoplasia. 
     
     
         13 . The polypeptide of  claim 12 , wherein the ATIA protein comprises the extracellular domain. 
     
     
         14 . The polypeptide of  claim 13 , wherein the extracellular domain comprises amino acid residues 600-673 of SEQ ID NO: 2. 
     
     
         15 . The polypeptide of  claim 12 , wherein the ATIA polypeptide comprises a sequence selected from the group consisting of: SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 9 and SEQ ID NO: 10, or fragments thereof. 
     
     
         16 . An isolated ATIA nucleic acid molecule, wherein the nucleic acid molecule encodes a polypeptide selected from  claim 12 ; or an isolated ATIA inhibitory nucleic acid molecule, wherein the inhibitory nucleic acid molecule specifically binds at least a fragment of a nucleic acid molecule encoding an ATIA protein; or An inhibitory nucleic acid molecule corresponding to at least a portion of an ATIA nucleic acid molecule that encodes an ATIA protein, wherein the inhibitory nucleic acid molecule is capable of altering the level of protein encoded by the ATIA nucleic acid molecule. 
     
     
         17 . A method of treating or preventing a neoplasia in a subject, the method comprising administering to a subject in need thereof an effective amount of a small molecule that alters expression of an ATIA polypeptide. 
     
     
         18 . A kit for the diagnosis of a neoplasia in a subject comprising a primer set to detect an ATIA nucleic acid molecule, or fragment thereof, and written instructions for use of the kit for diagnosis of a neoplasia. 
     
     
         19 . A method of altering the expression of an ATIA nucleic acid molecule or ATIA polypeptide in a cell, the method comprising contacting the cell with an effective amount of a compound capable of altering the expression of the ATIA nucleic acid molecule or ATIA polypeptide.