Molecular profiling of tumors

Abstract

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

What is claimed is: 
     
         1 . A system for generating a report identifying at least one therapeutic agent for an individual with a cancer comprising:
 a. at least one device configured to assay a plurality of molecular targets in a biological sample from the individual to determine molecular profile test values for each of the plurality of molecular targets, wherein the molecular targets comprise ERBB2, PTEN, TOP2A, TOPO1 and TS; and   b. at least one computer database comprising:
 i. a reference value for each of the plurality of molecular targets; and 
 ii. a listing of therapeutic agents with efficacy linked to a biological state of at least one member of the plurality of molecular targets; 
   c. a computer-readable program code comprising instructions to input the molecular profile test values and to compare each molecular profile test value with a corresponding reference value in (b)(i) to identify a biological state for each member of the plurality of molecular targets;   d. a computer-readable program code comprising instructions to identify at least one therapeutic agent from the listing of therapeutic agents in (b)(ii), wherein the biological state identified in (c) for at least one member of the plurality of molecular targets provides an indication of likely benefit of the at least one therapeutic agent for treating the cancer; and   e. a computer-readable program code comprising instructions to generate a report that comprises a listing of the at least one therapeutic agent identified in (d) and the biological state of each molecular target with efficacy linked thereto.   
     
     
         2 . The system of  claim 1 , wherein the molecular profile test values are input into the system from a location that is remote from the at least one computer database. 
     
     
         3 . The system of  claim 1 , wherein the molecular profile test values are input into the system over an internet connection. 
     
     
         4 . The system of  claim 1 , wherein the report is in electronic or paper format. 
     
     
         5 . The system of  claim 1 , wherein the at least one computer database further comprises data corresponding to at least one clinical trial linked to the biological state of at least one member of the plurality of molecular targets. 
     
     
         6 . The system of  claim 1 , wherein the at least one computer database further comprises prognostic data corresponding to the biological state of at least one member of the plurality of molecular targets. 
     
     
         7 . The system of  claim 1 , wherein the biological state for each of the plurality of molecular targets comprises at least one of a sequence, expression level or gene copy number. 
     
     
         8 . The system of  claim 1 , wherein the reference value for each of the plurality of molecular targets comprises at least one of a sequence, expression level or gene copy number. 
     
     
         9 . The system of  claim 1 , wherein the biological sample comprises a cell, tissue sample, bodily fluid, blood sample or combination thereof. 
     
     
         10 . The system of  claim 1 , wherein each reference value is obtained from at least one normal individual that does not have cancer. 
     
     
         11 . The system of  claim 1 , wherein the individual has undergone at least one treatment for the cancer. 
     
     
         12 . The system of  claim 1 , wherein determining the molecular profile test values for ERBB2, PTEN, TOP2A, TOPO1 and TS comprises immunohistochemistry and determining the molecular profile test values for ERBB2 further comprises in situ hybridization. 
     
     
         13 . The system of  claim 1 , wherein the plurality of molecular targets further comprises BRCA2, EGFR, KIT, PDGFRA, TP53 and VHL. 
     
     
         14 . The system of  claim 13 , wherein determining the molecular profile test values for BRCA2, EGFR, KIT, PDGFRA, TP53 and VHL comprises DNA sequencing. 
     
     
         15 . The system of  claim 1 , wherein the plurality of molecular targets further comprises RRM1, BRCA1 and KDR. 
     
     
         16 . The system of  claim 15 , wherein determining the molecular profile test values for RRM1 comprises immunohistochemistry and determining the molecular profile test values for BRCA1 and KDR comprises DNA sequencing. 
     
     
         17 . The system of  claim 1 , wherein the plurality of molecular targets further comprises BRAF, ERBB4, ERCC1, KRAS, MET, MGMT and PIK3CA. 
     
     
         18 . The system of  claim 17 , wherein determining the molecular profile test values for ERCC1 and MGMT comprises immunohistochemistry and determining the molecular profile test values for BRAF, ERBB4, KRAS, MET and PIK3CA comprises DNA sequencing. 
     
     
         19 . The system of  claim 1 , wherein the cancer comprises a sarcoma. 
     
     
         20 . The system of  claim 1 , wherein the report further comprises a listing of: 1) at least one additional therapeutic agent wherein the biological state for at least one member of the plurality of molecular targets identified in (c) provides an indication of likely lack of benefit of the at least one therapeutic agent for treating the individual; and 2) the biological state of each molecular target with efficacy linked to the at least one additional therapeutic agent. 
     
     
         21 . The system of  claim 1 , wherein the at least one device configured to assay the plurality of molecular targets is configured to perform at least one of polymerase chain reaction (PCR), pyrosequencing, real-time PCR, sequencing, NextGen sequencing, methylation specific PCR (MSPCR), restriction fragment length polymorphism (RFLP) analysis, immunohistochemistry (IHC), immunoassay, an expression microarray, a comparative genomic hybridization (CGH) microarray, a single nucleotide polymorphism (SNP) microarray, in-situ hybridization (ISH), fluorescent in-situ hybridization (FISH), and a proteomic array. 
     
     
         22 . The system of  claim 1 , wherein the at least one device configured to assay the plurality of molecular targets is configured to perform at least one of gene expression analysis, nucleic acid sequence analysis, nucleic acid methylation analysis and proteomic analysis. 
     
     
         23 . The system of  claim 1 , wherein the at least one device configured to assay the plurality of molecular targets is configured to identify at least one of a mutation, polymorphism, deletion, insertion, substitution, translocation, fusion, break, duplication, amplification or repeat in a nucleic acid sequence corresponding to at least one of the molecular targets.