FILIP1L compositions and methods for treating cancer

Abstract

A purified DOC1 polypeptide comprising a fragment of SEQ ID NO: 1 is provided, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence. A method of inhibiting angiogenesis in a subject is provided comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting angiogenesis. A method of inhibiting tumor growth in a subject is provided comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting tumor growth.

What is claimed is: 
     
         1 . A nucleic acid encoding a DOC1 polypeptide comprising a fragment of SEQ ID NO: 1, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, or encoding a polypeptide comprising an amino acid sequence that is at least about 95% identical to the DOC1 polypeptide. 
     
     
         2 . A vector comprising the nucleic acid of  claim 1 . 
     
     
         3 . A host cell comprising the vector of  claim 2 . 
     
     
         4 . A method of inhibiting angiogenesis in a subject comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting angiogenesis. 
     
     
         5 . The method of  claim 4 , wherein the nucleic acid is administered locally. 
     
     
         6 . The method of  claim 4 , wherein the nucleic acid is administered systemically. 
     
     
         7 . The method of  claim 4 , wherein the nucleic acid is administered in a vector. 
     
     
         8 . The method of  claim 4 , wherein the nucleic acid encodes SEQ ID NO: 1. 
     
     
         9 . The method of  claim 4 , wherein the nucleic acid encodes a fragment of SEQ ID NO: 1. 
     
     
         10 . The method of  claim 9 , wherein the fragment of SEQ ID NO: 1 is selected from the group consisting of amino acids amino acids 1-790 of SEQ ID NO: 1, amino acids 1-650 of SEQ ID NO: 1, amino acids 1-512 of SEQ ID NO: 1, amino acids 65-893 of SEQ ID NO: 1, amino acids 127-893 of SEQ ID NO: 1, and amino acids 127-650 of SEQ ID NO: 1. 
     
     
         11 . A method of inhibiting tumor growth in a subject comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting tumor growth. 
     
     
         12 . The method of  claim 11 , wherein the nucleic acid is administered locally. 
     
     
         13 . The method of  claim 11 , wherein the nucleic acid is administered systemically. 
     
     
         14 . The method of  claim 19 , wherein the nucleic acid is administered in a vector. 
     
     
         15 . The method of  claim 11 , wherein the nucleic acid encodes SEQ ID NO: 1. 
     
     
         16 . The method of  claim 11 , wherein the nucleic acid encodes a fragment of SEQ ID NO: 1. 
     
     
         17 . The method of  claim 16 , wherein the fragment of SEQ ID NO: 1 is selected from the group consisting of amino acids 1-790 of SEQ ID NO: 1, amino acids 1-650 of SEQ ID NO: 1, amino acids 1-512 of SEQ ID NO: 1, amino acids 65-893 of SEQ ID NO: 1, amino acids 127-893 of SEQ ID NO: 1, and amino acids 127-650 of SEQ ID NO: 1. 
     
     
         18 . An antibody that specifically binds to a DOC1 polypeptide comprising a fragment of SEQ ID NO: 1, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, with the proviso that the antibody does not specifically bind a fragment consisting of amino acids 3-52 or amino acids 510-893 of SEQ ID NO:1. 
     
     
         19 . The antibody of  claim 18 , wherein the antibody specifically binds to a polypeptide selected from the group consisting of amino acids amino acids 1-790 of SEQ ID NO: 1, amino acids 1-650 of SEQ ID NO: 1, amino acids 1-512 of SEQ ID NO: 1, amino acids 65-893 of SEQ ID NO: 1, amino acids 127-893 of SEQ ID NO: 1, and amino acids 127-650 of SEQ ID NO: 1. 
     
     
         20 . A method for classifying a cancer in a subject comprising:
 a) contacting a test sample from a subject with an anti-DOC1 antibody;   b) detecting the binding of the anti-DOC1 antibody to a DOC1 polypeptide in the sample;   c) comparing the expression level of the DOC1 polypeptide in the test sample with the expression level of a DOC1 polypeptide in a reference sample for which a cancer classification is known; and   d) identifying a difference, if present, in the expression level of the DOC1 polypeptide in the test sample and reference sample, thereby classifying the cancer in the subject.   
     
     
         21 . The method of  claim 20 , wherein a difference in the expression level of the DOC1 polypeptide in the test sample as compared to the reference sample indicates that the test sample has a different classification as the reference sample. 
     
     
         22 . The method of  claim 20 , wherein a similar expression level of the DOC1 polypeptide in the sample as compared to the reference sample indicates that the test sample has the same classification as the reference sample. 
     
     
         23 . The method of  claim 20 , wherein the reference sample is a sample from a subject with a known classification. 
     
     
         24 . The method of  claim 20 , wherein the reference sample is from a database. 
     
     
         25 . The method of  claim 20 , wherein the reference sample is a reference sample classified as a normal sample. 
     
     
         26 . The method of  claim 20 , wherein the reference sample is a reference sample classified as cancerous. 
     
     
         27 . A method for identifying a stage of cancer in a subject comprising:
 a) contacting a test sample from a subject with an anti-DOC1 antibody;   b) detecting the binding of the anti-DOC1 antibody to a DOC1 polypeptide in the sample;   c) comparing the expression level of the DOC1 polypeptide in the test sample with the expression level of a DOC1 polypeptide in a reference sample for which a stage of cancer is known; and   d) identifying a difference, if present, in the expression level of the DOC1 polypeptide in the test sample and reference sample, thereby identifying the stage of cancer in the subject.   
     
     
         28 . The method of  claim 27 , wherein a difference in the expression level of the DOC1 polypeptide in the test sample as compared to the reference sample indicates that the test sample has a different stage of cancer than the reference sample. 
     
     
         29 . The method of  claim 27 , wherein a similar expression level of the DOC1 polypeptide in the test sample as compared to the reference sample indicates that the test sample has the same stage of cancer as the reference sample. 
     
     
         30 . The method of  claim 27 , wherein the reference sample is a sample from a patient with a known stage of cancer. 
     
     
         31 . The method of  claim 27 , wherein the reference sample is from a database. 
     
     
         32 . A method of determining the efficacy of an anti-cancer treatment comprising:
 a) determining the expression level of a DOC1 polypeptide in a sample obtained from the subject;   b) administering the anti-cancer treatment;   c) determining the expression level of a DOC1 polypeptide in a sample obtained from the subject after administration of the anti-cancer treatment; and   d) comparing the expression level of the DOC1 polypeptide in the sample obtained after the anti-cancer treatment with the sample obtained in step a) such that if there is a change in the expression level of the DOC1 polypeptide in the sample obtained after the anti-cancer treatment as compared to the sample obtained before administration of the anti-cancer treatment, wherein the change is associated with an improvement in the subject, the anti-cancer therapeutic is an effective anti-cancer therapeutic.   
     
     
         33 . The method of  claim 32 , wherein the change is an increase in the expression levels of the DOC1 polypeptide. 
     
     
         34 . The method of  claim 32 , wherein the change is a decrease in the expression levels of the DOC1 polypeptide. 
     
     
         35 . A method of identifying a modulator of DOC1 expression comprising:
 a) contacting a cell that is capable of expressing DOC1 with a putative modulator;   b) measuring DOC1 expression, wherein a change in DOC1 expression in the cell of step a) as compared to a cell that was not contacted with the putative modulator indicates the presence of a modulator of DOC1 expression.   
     
     
         36 . The method of  claim 35 , wherein the change in DOC1 expression is an increase in DOC1 expression. 
     
     
         37 . The method of  claim 35 , wherein the change in DOC1 expression is a decrease in DOC1 expression. 
     
     
         38 . The method of  claim 35 , wherein DOC1 expression is measured by amplifying a DOC1 nucleic acid. 
     
     
         39 . The method of  claim 35 , wherein DOC1 expression is measured by detecting a DOC1 polypeptide. 
     
     
         40 . A purified DOC1 polypeptide comprising a fragment of SEQ ID NO: 2, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, and the fragment is at least 51 amino acids in length. 
     
     
         41 . A purified DOC1 polypeptide comprising a fragment of SEQ ID NO: 3, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, and the fragment is at least 51 amino acids in length. 
     
     
         42 . A purified DOC1 polypeptide comprising a fragment of SEQ ID NO: 1, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, and the fragment comprises amino acids 127-512 of SEQ ID NO:1.