K-ras mutations and anti-EGFr antibody therapy

Abstract

The present application relates to K-ras mutations, to polynucleotides encoding mutant K-ras polypeptides, and to methods of identifying K-ras mutations. The present application also relates to methods of diagnosing cancer; and methods and kits for predicting the usefulness of anti-EGFr specific binding agents in the treatment of tumors.

1 . A method of predicting whether a patient will be nonresponsive to treatment with a specific binding agent to an EGFr polypeptide, comprising determining the presence or absence of a K-ras mutation in a tumor of the patient, wherein the K-ras mutation is in codon 12 or codon 13 or codon 20; and wherein if a K-ras mutation is present, the patient is predicted to be nonresponsive to treatment with a specific binding agent to an EGFr polypeptide. 
     
     
         2 . The method of  claim 1 , wherein the determining the presence or absence of a K-ras mutation in a tumor comprises amplifying a K-ras nucleic acid from the tumor and sequencing the amplified nucleic acid. 
     
     
         3 . The method of  claim 1 , wherein the specific binding agent to an EGFr polypeptide is an antibody to EGFr. 
     
     
         4 . The method of  claim 3 , wherein the antibody to EGFr is panitumumab. 
     
     
         5 . The method of  claim 1 , wherein the determining the presence or absence of a K-ras mutation in a tumor comprises detecting a mutant K-ras polypeptide in a sample of the tumor using a specific binding agent to a mutant K-ras polypeptide. 
     
     
         6 . The method of  claim 1 , wherein the K-ras mutation is selected from G12S, G12V, G12D, G12A, G12C, G13A, G13D, and T20M. 
     
     
         7 . A method of predicting whether a tumor will be nonresponsive to treatment with a specific binding agent to an EGFr polypeptide, comprising determining the presence or absence of a K-ras mutation in a sample of said tumor, wherein the K-ras mutation is in codon 12 or codon 13 or codon 20; and wherein the presence of the K-ras mutation indicates that the tumor will be nonresponsive to treatment with a specific binding agent to an EGFr polypeptide. 
     
     
         8 . The method of  claim 7 , wherein the determining the presence or absence of a K-ras mutation in a sample of said tumor comprises amplifying K-ras nucleic acid from the tumor and sequencing the amplified nucleic acid. 
     
     
         9 . The method of  claim 7 , wherein the specific binding agent to an EGFr polypeptide is an antibody to EGFr. 
     
     
         10 . The method of  claim 9 , wherein the antibody to EGFr is panitumumab. 
     
     
         11 . The method of  claim 7 , wherein the determining the presence or absence of a K-ras mutation in the sample of said tumor comprises detecting a mutant K-ras polypeptide using a specific binding agent to a mutant K-ras polypeptide. 
     
     
         12 . The method of  claim 7 , wherein the K-ras mutation is selected from G12S, G12V, G12D, G12A, G12C, G13A, G13D, and T20M.