MOLECULAR PROFILING OF TUMORS
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.
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 the plurality of molecular targets, wherein the molecular targets comprise AR, ERBB2, PTEN, and TOP2A; 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 AR, ERBB2, PTEN, and TOP2A 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 BRCA1 and KDR.
16 . The system of claim 15 , wherein 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 and PIK3CA.
18 . The system of claim 17 , wherein determining the molecular profile test values for ERCC1 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 prostate cancer.
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.