Methods and compositions for the diagnosis and treatment of cancer

Abstract

Methods and compositions are provided for the diagnosis and treatment of colorectal cancers associated with amplification or overexpression of the FGFR2 gene.

1 . A method of diagnosing the presence of a colorectal cancer in a mammal, the method comprising
 a) obtaining a test colorectal sample or a colorectal cancer sample from the mammal;   b) detecting the copy number of the FGFR2 gene in the test colorectal sample or colorectal cancer sample;   c) comparing said copy number of the FGFR2 gene detected in step b) with the copy number of the FGFR2 gene in a control normal sample; and   
       d) identifying the mammal as having colorectal cancer when a higher copy number of the FGFR2 is detected relative to a control normal sample. 
     
     
         2 . The method of  claim 1 , wherein detecting whether the FGFR2 gene is amplified comprises detecting whether the copy number of the FGFR2 gene is increased by at least 5-fold. 
     
     
         3 - 22 . (canceled) 
     
     
         23 . A method of treating a colorectal cancer associated with amplification of the FGFR2 gene in an individual having the colorectral cancer, the method comprising
 a) obtaining a test colorectal sample or a colorectal cancer sample from the mammal;   b) detecting the copy number of the FGFR2 gene in the test colorectal sample or colorectal cancer sample;   c) comparing said copy number of the FGFR2 gene detected in step b) with the copy number of the FGFR2 gene in a control normal sample;   d) identifying that the individual having a colorectal cancer will respond to a therapeutic that targets FGFR2 when a higher copy number of the FGFR2 gene is detected relative to a control normal sample; and   e) administering to said individual having the colorectal cancer associated with amplification of the FGFR2 gene, an effective amount of a pharmaceutical formulation comprising a therapeutic that targets FGFR2 or the FGFR2 gene.   
     
     
         24 . The method of  claim 23 , wherein the FGFR2 antagonist is an anti-FGFR2 antibody. 
     
     
         25 . The method of  claim 24 , wherein the anti-FGFR2 antibody binds to the extracellular domain of FGFR2. 
     
     
         26 . The method of  claim 24 , wherein the anti-FGFR2 antibody is an antibody fragment. 
     
     
         27 . The method of  claim 24 , wherein the anti-FGFR2 antibody is a chimeric or humanized antibody. 
     
     
         28 . The method of  claim 24 , wherein the anti-FGFR2 antibody is a human antibody. 
     
     
         29 . The method of  claim 23 , wherein the FGFR2 antagonist is an organic molecule that binds to FGFR2. 
     
     
         30 . The method of  claim 23 , wherein the FGFR2 antagonist is an oligopeptide that binds to FGFR2. 
     
     
         31 . The method of  claim 23 , wherein the FGFR2 antagonist is a soluble form of FGFR2. 
     
     
         32 . The method of  claim 23 , wherein the FGFR2 antagonist is an antisense nucleic acid of 10-30 nucleotides in length that binds to and reduces expression of a nucleic acid encoding FGFR2. 
     
     
         33 . The method of  claim 23 , wherein the pharmaceutical formulation is administered in combination with at least one additional therapeutic agent and/or adjuvant. 
     
     
         34 . The method of  claim 33 , wherein the additional therapeutic agent is an unconjugated cytotoxic agent, a chemotherapeutic agent, or a growth inhibitory agent. 
     
     
         35 . The method of  claim 34 , wherein the chemotherapeutic agent is an agent or a combination of agents used in the treatment of colorectal cancer. 
     
     
         36 . The method of  claim 35 , wherein the agents include, but are not limited to, fluorouracil (5FU) alone or in combination with leucovorin or levamisole; edrocolomab; irinotecan; oxaliplatin; raltitrexed; and fluoropyrimidines. 
     
     
         37 . A method for determining whether an individual having a colorectal cancer will respond to a therapeutic that targets FGFR2 or the FGFR2 gene, the method comprising
 a) obtaining a test colorectal sample or a colorectal cancer sample from the mammal;   b) detecting the copy number of the FGFR2 gene in the test colorectal sample or colorectal cancer sample;   c) comparing said copy number of the FGFR2 gene detected in step b) with the copy number of the FGFR2 gene in a control normal sample; and   d) identifying that the individual having a colorectal cancer will respond to a therapeutic that targets FGFR2 when a higher copy number of the FGFR2 gene is detected relative to a control normal sample.   
     
     
         38 . The method of  claim 37 , wherein the therapeutic is (a) an FGFR2 antagonist, (b) a cytotoxic anti-FGFR2 antibody, or (c) an immunoconjugate comprising an anti-FGFR2 antibody and a cytotoxic agent. 
     
     
         39 . The method of  claim 37 , wherein determining whether the FGFR2 gene is amplified comprises detecting whether the copy number of the FGFR2 gene is increased by at least 5-fold. 
     
     
         40 . The method of  claim 37 , wherein the amplification of the FGFR2 gene is detected using an amplification assay or a hybridization assay.