Methods for personalizing cancer treatment

Abstract

Personalized medicine involves the use of a patient's molecular markers to guide treatment regimens for the patient. The scientific literature provides multiple examples of correlations between drug treatment efficacy and the presence or absence of molecular markers in a patient sample. Methods are provided herein that permit efficient dissemination of scientific findings regarding treatment efficacy and molecular markers found in patient tumors to health care providers.

1 - 75 . (canceled) 
     
     
         76 . A method of determining personalized cancer treatment options for a subject, the method comprising:
 a. obtaining a sample from a subject, wherein the sample comprises molecular markers from a tumor cell;   b. determining a status of the molecular markers, wherein the molecular markers comprise at least four of the molecular markers selected from the group consisting of c-kit, Kras, BRAF, EGFR, microsatellite sequence, chromosome 18q, thymidylate synthase, and Topo1; and   c. stratifying one or more cancer drug treatment options in a report based on the status of the molecular markers.   
     
     
         77 . The method of  claim 76 , wherein the at least four molecular markers comprise c-kit, Kras, BRAF, and EGFR. 
     
     
         78 . The method of  claim 76 , wherein the at least four molecular markers comprise c-kit, and the c-kit comprises an activating mutation. 
     
     
         79 . The method of  claim 78 , wherein the activating mutation is in a juxtamembrane domain of c-kit. 
     
     
         80 . The method of  claim 76 , wherein the at least four molecular markers comprise c-kit, and the c-kit is not expressed. 
     
     
         81 . The method of  claim 78 , wherein the one or more cancer drug treatment options comprise imatinib mesylate. 
     
     
         82 . The method of  claim 76 , wherein the at least four molecular markers comprise Kras, and wherein the Kras comprises a mutation in exon 2. 
     
     
         83 . The method of  claim 82 , wherein the mutation in exon 2 is in codon 12 or 13. 
     
     
         84 . The method of  claim 82 , wherein the one or more cancer drug treatment options comprise cetuximab or panitumumab. 
     
     
         85 . The method of  claim 76 , wherein the at least four molecular markers comprise BRAF, and the BRAF encodes a V600E mutation. 
     
     
         86 . The method of  claim 85 , wherein the one or more cancer drug treatment options comprise cetuximab or panitumumab. 
     
     
         87 . The method of  claim 76 , wherein the at least four molecular markers comprise microsatellite sequence, and the microsatellite sequence displays low-frequency microsatellite instability. 
     
     
         88 . The method of  claim 76 , wherein the at least four molecular markers comprise microsatellite sequence, and the microsatellite sequence displays high-frequency microsatellite instability. 
     
     
         89 . The method of  claim 87 , wherein the one or more cancer drug treatment options comprise fluorouracil-based adjuvant chemotherapy. 
     
     
         90 . The method of  claim 76 , wherein the at least four molecular markers comprise EGFR, and the EGFR comprises a copy number increase relative to normal. 
     
     
         91 . The method of  claim 76 , wherein the at least four molecular markers comprise EGFR, and the EGFR comprises a mutation in exons 18-21. 
     
     
         92 . The method of  claim 90 , wherein the one or more cancer drug treatment options comprise cetuximab or panitumumab. 
     
     
         93 . The method of  claim 76 , wherein the at least four molecular markers comprise chromosome 18q, and the subject comprises chromosome 18q allelic loss. 
     
     
         94 . The method of  claim 93 , wherein the one or more cancer drug treatment options comprise adjuvant therapy. 
     
     
         95 . The method of  claim 76 , wherein the at least four molecular markers comprise thymidylate synthase, and the thymidylate synthase comprises levels that are low. 
     
     
         96 . The method of  claim 76 , wherein the at least four molecular markers comprise thymidylate synthase, and the thymidylate synthase comprises levels that are high. 
     
     
         97 . The method of  claim 95 , wherein the one or more cancer drug treatment options comprise 5-FU. 
     
     
         98 . The method of  claim 76 , wherein the at least four molecular markers comprise Topo1, and the Topo1 comprises expression that is moderate to high. 
     
     
         99 . The method of  claim 98 , wherein the one or more cancer drug treatment options comprise irinotecan. 
     
     
         100 . The method of  claim 76 , wherein the one or more cancer drug treatment options comprise imatinib mesylate, cetuximab, panitumumab, bevacizumab, 5-FU, capecitabine, or irinotecan. 
     
     
         101 . The method of  claim 76 , wherein the sample comprises a tumor biopsy. 
     
     
         102 . The method of  claim 76 , wherein the sample comprises a cell-free sample. 
     
     
         103 . The method of  claim 76 , wherein the tumor cell is a colon cancer, a bone cancer, a breast cancer, a central nervous system cancer, a gastric cancer, a cervical cancer, an esophageal cancer, a head and neck cancer, a kidney cancer, a skin cancer, a lung cancer, or a carcinoma. 
     
     
         104 . The method of  claim 103 , wherein the tumor cell is a colon cancer. 
     
     
         105 . The method of  claim 76 , wherein the determining comprises nucleic acid amplification, de novo DNA sequencing, fluorescent in-situ hybridization (FISH), quantitative PCR (qPCR), digital PCR, or immunohistochemistry (IHC). 
     
     
         106 . The method of  claim 105 , wherein the determining comprises de novo DNA sequencing. 
     
     
         107 . The method of  claim 106 , wherein the de novo DNA sequencing comprises use of reversibly terminating nucleotides. 
     
     
         108 . The method of  claim 105 , wherein the determining comprises digital PCR. 
     
     
         109 . The method of  claim 76 , wherein the molecular markers comprise nucleic acid sequence. 
     
     
         110 . The method of  claim 109 , wherein the determining comprises determining an absence of one or more mutations or a presence of the one or more mutations in the molecular markers. 
     
     
         111 . The method of  claim 110 , wherein the one or more mutations comprise a de novo mutation, nonsense mutation, missense mutation, silent mutation, frameshift mutation, insertion, substitution, point mutation, deletion, rearrangement, amplification, chromosomal translocation, interstitial deletion, chromosomal inversion, loss of heterozygosity, loss of function mutation, gain of function mutation, dominant negative mutation, or lethal mutation. 
     
     
         112 . The method of  claim 111 , wherein the one or more mutations comprise a substitution, insertion, deletion, amplification, or rearrangement. 
     
     
         113 . The method of claim  1 , wherein the sample comprises greater than 15% tumor.