Methods of treating cancer patients with farnesyltransferase inhibitors

Abstract

The present invention relates to the field of molecular biology and cancer biology. Specifically, the present invention relates to methods of treating a subject with a farnesyltransferase inhibitor (FTI) that include determining whether the subject is likely to be responsive to the FTI treatment based on HRAS mutation status in the subject.

1 - 50 . (canceled) 
     
     
         51 . A method of treating EGFR inhibitor-refractory lung squamous cell carcinoma (lung SCC) in a subject, wherein the lung SCC has an HRAS mutation, comprising administering to the subject a farnesyltransferase inhibitor (FTI). 
     
     
         52 . The method of  claim 51 , wherein said HRAS mutation comprises an amino acid substitution at a codon selected from a group consisting of G12, G13, Q61, Q22, K117, A146, and any combination thereof. 
     
     
         53 . The method of  claim 51 , wherein said lung SCC does not have K-Ras mutation or N-Ras mutation. 
     
     
         54 . The method of  claim 53 , wherein said lung SCC has wild type K-Ras and wild type N-Ras. 
     
     
         55 . The method of  claim 51 , wherein said lung SCC is HPV negative. 
     
     
         56 . The method of  claim 51 , wherein said lung SCC is at an advanced stage or metastatic. 
     
     
         57 . The method of  claim 51 , wherein said lung SCC is relapsed lung SCC. 
     
     
         58 . The method of  claim 51 , wherein the EGFR inhibitor is cetuximab. 
     
     
         59 . The method of  claim 51 , wherein the FTI is tipifarnib. 
     
     
         60 - 75 . (canceled) 
     
     
         76 . A method of treating an lung SCC in a subject, wherein a sample from the subject has an HRAS mutation, and wherein the subject has never been treated with an EGFR inhibitor, comprising
 administering a therapeutically effective amount of an FTI to said subject and not administering an EGFR inhibitor.   
     
     
         77 . The method of  claim 76 , wherein said HRAS mutation comprises an amino acid substitution at a codon selected from a group consisting of G12, G13, Q61, Q22, K117, A146, and any combination thereof. 
     
     
         78 . The method of  claim 76 , further comprising determining the presence or absence of a K-Ras mutation or a N-Ras mutation, wherein said sample does not have K-Ras mutation or N-Ras mutation. 
     
     
         79 . The method of  claim 78 , wherein said sample has wild type K-Ras and wild type N-Ras. 
     
     
         80 . The method of  claim 76 , wherein said sample is a tissue biopsy or a tumor biopsy. 
     
     
         81 . (canceled) 
     
     
         82 . The method of  claim 76 , wherein determining the presence or absence of a HRAS mutation comprises: (i) analyzing nucleic acids obtained from said sample, wherein said Ras mutation is determined by sequencing, Polymerase Chain Reaction (PCR), DNA microarray, Mass Spectrometry (MS), Single Nucleotide Polymorphism (SNP) assay, denaturing high-performance liquid chromatography (DHPLC), or Restriction Fragment Length Polymorphism (RFLP) assay; or (ii) analyzing proteins obtained from said sample. 
     
     
         83 - 86 . (canceled) 
     
     
         87 . The method of  claim 76 , wherein said lung SCC is HPV negative. 
     
     
         88 . The method of  claim 76 , wherein said lung SCC is at an advanced stage or metastatic. 
     
     
         89 . The method of  claim 76 , wherein said lung SCC is relapsed lung SCC. 
     
     
         90 . The method of  claim 76 , wherein the EGFR inhibitor is cetuximab. 
     
     
         91 . The method of  claim 76 , wherein the FTI is tipifarnib.