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 genotyping and expression profiling of certain immunological genes and RAS mutation status in the subject.

1 - 17 . (canceled) 
     
     
         18 . A method of treating a solid tumor in a subject comprising
 (a) determining the presence or absence of a H-Ras mutation in a sample from said subject, and subsequently   (b) administering a therapeutically effective amount of a farnesyltransferase inhibitor (FTI) to said subject if said sample is determined to have a H-Ras mutation.   
     
     
         19 . The method of  claim 18 , wherein said H-Ras mutation comprises an amino acid substitution at a codon selected from a group consisting of G12, G13, Q61, and any combination thereof. 
     
     
         20 . The method of  claim 18 , 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. 
     
     
         21 . The method of  claim 18 , wherein said solid tumor is selected from the group consisting of hepatocelluar carcinoma, head and neck cancer, salivary gland tumor, thyroid tumor, urothelial cancer, breast cancer, melanoma, gastric cancer, pancreatic cancer, and lung cancer. 
     
     
         22 . The method of  claim 18 , wherein the FTI is tipifarnib. 
     
     
         23 . A method of treating a cancer in a subject comprising
 (a) determining the presence or absence of a Ras mutation in a sample from said subject, said Ras mutation comprising a K-Ras mutation or a N-Ras mutation, and subsequently   (b) administering a therapeutically effective amount of a farnesyltransferase inhibitor (FTI) to said subject if said sample is determined to lack said K-Ras mutation or said N-Ras mutation.   
     
     
         24 . The method of  claim 23 , wherein said K-Ras mutation comprises an amino acid substitution at a codon selected from a group consisting of G12, G13, Q61, and any combination thereof. 
     
     
         25 . The method of  claim 23 , wherein said N-Ras mutation comprises an amino acid substitution at a codon selected from a group consisting of G12, G13, Q61, and any combination thereof. 
     
     
         26 . The method of  claim 23 , wherein said sample does not have K-Ras mutation or N-Ras mutation. 
     
     
         27 . The method of  claim 26 , wherein said sample has wild type K-Ras and wild-type N-Ras. 
     
     
         28 . The method of  claim 23 , wherein said Ras mutation further comprises an H-Ras mutation, and said sample is determined to have said H-Ras mutation. 
     
     
         29 . The method of  claim 23 , wherein said cancer is myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML), natural killer cell lymphoma (NK lymphoma), natural killer cell leukemia (NK leukemia), cutaneous T-Cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL), chronic myeloid leukemia (CML) or a solid tumor. 
     
     
         30 . A method of treating cancer in a subject comprising
 (a) KIR typing said subject, wherein said subject is a carrier of KIR2DS2 or KIR2DS5, and   (b) administering a therapeutically effective amount of a FTI to said subject.   
     
     
         31 . The method of  claim 30 , wherein said subject is a carrier of KIR2DS2. 
     
     
         32 . The method of  claim 30 , wherein said subject is a carrier of KIR2DS5. 
     
     
         33 . The method of  claim 30 , further comprising HLA typing said subject, wherein said subject is a carrier of HLA-C2. 
     
     
         34 . The method of  claim 33 , wherein said subject is a carrier of KIR2DS2 and HLA-C2. 
     
     
         35 . The method of  claim 33 , wherein said carrier of HLA-C2 is homozygous for HLAC2. 
     
     
         36 . The method of  claim 30 , wherein said cancer is acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), natural killer cell lymphoma (NK lymphoma), natural killer cell leukemia (NK leukemia), cutaneous T-Cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL), chronic myeloid leukemia (CML) or a solid tumor. 
     
     
         37 . The method of  claim 36 , wherein said cancer is lower risk MDS.