Genomic testing has proven to be effective to accurately diagnose and guide treatment of breast and colorectal cancer. Results from these tests are used to provide a molecular portrait of an individual patient’s cancer. This in turn allows the clinician to determine the origin of the cancer, the likelihood of metastasis, specific drug responsiveness and likelihood of reoccurrence.

The conventional method of diagnosis looks at the general classification of the cancers according to the gross morphological appearance of the cells and surrounding tissues. Patients are then treated based on broad diagnostic groups. However, conventional understanding doesn’t explain why pathologically identical tumours have been found to respond differently to the same treatment. It is this challenge that led to the development of molecular tumour profiling tests for not only breast and colorectal cancers, but all solid tumours.

Since 2008, three companies have introduced commercial tests that provide molecular profiles for individual patient tumours. The tests are: Caris Target Now® from Caris Life Services; OncInsights® from Intervention Insights; and a profiling service from GeneKey. All three tests are conducted in the United States, although some private health insurers in Australia will subsidise these tests for their patients. The tests are marketed directly to oncologists as tools to assist in the selection of appropriate drugs for the patient’s specific tumour. They provide the oncologist with the profile of the tumour as well as a list of drugs that the tumour may respond to, identified using the molecular features of the specific tumour.

The tests use various different methods, including matching overexpressed genes with drugs and looking into complex signalling pathways and networks in tumour cells. Caris Target Now® is the most widely used test to date. It uses immunohistochemistry to detect 20 cancer-related proteins. The tumour sections are stained with antibodies against target proteins. By using an Illumina oligonucleotide microarray, the expression of approximately 80 genes are able to be determined. The test also uses fluorescence in situ hybridisation, DNA sequencing and polymerase chain reactions. The ultimate goal is to detect abnormal gene expression in the biopsy. The abnormal genes are matched with drugs based on evidence in scientific literature which indicates the drug which the abnormal gene may be responsive to. The report gives a list of the drugs and relevant literature, which is weighted according to its relevance. It has been described by Dr Alan Wright, M.D and Vice President of Caris Life Services to be “more a literature aggregation profiling platform than an isolated test.” There is no specific treatment recommended in the report.

There has been one research study, the Bisgrove Trial, conducted on the Caris Target Now® test. It indicated that slightly more than 27% of 66 patients, whose oncologist used Caris Target Now® to determine their treatment, had a progression-free survival lasting at least 30% longer than that of conventional treatments. Daniel Van Hoff, the lead author and investigator of this study said the study results were promising.

At the European Cancer Congress 2013, Dr Andrew Dean presented an abstract of findings on the use of Caris Target Now® for his patients at St John of God Hospital Subiaco, Western Australia. He had a cohort of ten patients with rare cancers and thirty heavily pre-treated patients with advanced cancer. All patients in both cohorts had ECOG (Eastern Co-operative Oncology Group) performance scores of less than two. The rare cancer cohort included: ethmoid sinus, adrenal cortex adenocarcinoma, anaplastic thyroid, fibrosarcoma, astroblastoma, cervical carcinosarcoma, pseudopapillary mucinous neoplasm, endometrial stromal sarcoma and medullary thyroid. The heavily pre-treated cohort included: cervical, gall bladder, skin (Merkel), colorectal, lung, pancreatic, gastric, breast, ovarian, melanoma, oesophageal, cholangiocarcinoma and mesothelioma. Out of the ten patients in the rare cohort, two patients showed disease progression, two achieved non-evaluable disease and the remaining six showed clinical benefit. In the heavily pre-treated cohort, seventeen of the patients showed clinical benefits and the remaining thirteen had disease progression. The sustained clinical responses ranged from 140 days to 365 days. Dr Dean concluded that this data lent support to the use of molecular profiling in identifying possible treatments in patients with limited treatment options and poor prognosis.

OncSight® uses gene expression to match tumours to drugs. The difference with this test is that it uses analytical methods to take advantage of current knowledge of signalling pathways. It uses an Affymetrix chip to measure the RNA of 25,000 genes. This almost covers the whole genome spectrum. Similarly to Caris Target Now®, it identifies the biomarkers and their response to certain drugs according to published literature. It also links gene expression levels to drug response.

A point of difference is that it incorporates systems biology approaches. The downfall of gene expression profiling is that it is unable to differentiate between driver genes and passenger genes. Driver genes may actively promote tumour growth, whilst passenger genes do not. Systems biology looks at the signalling pathways and networks in these genes. Connectivity maps are used to look at the expression patterns of the tumour and drugs that are most likely to influence these expressions based on cell line experiments. The oncologist receives a summary report which lists possible responsive drugs, their scores and literature evidence. There is also no specific drug recommendation.

GeneKey looks at the entire genome mRNA expression profiling and copy number variant detection. It also looks at whole exome DNA sequencing. Fewer people have used this test as it costs $30,000 – $35,000. However, Dr Raphael Lehrer, GeneKey Chief Scientist, has said that, “using whole-exome sequencing along with gene expression and copy number profiling provides redundancy and thus greater confidence in the data.” By looking at all pathways, useful drugs that are not cancer related have been identified. Again, the final report does not include specific recommendations.

These commercialised tests have potential to guide treatment; however, until there are randomised trials for these individual tests, there is not enough data to demonstrate that they provide conclusive benefit for patients. These trials should occur before these tests are used routinely to look at alternative cancer treatment options. Tumour profiling offers a potential for the future, the time frame as to when this occurs will be dependent on clinical trials and their results.


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  2. Dean A, Wallace R. Clinical application of molecular profiling in selecting treatment for advanced refractory and rare solid tumours: an Australian experience [abstract 955]. Eur J Cancer. 2013;49 (Suppl.2).
  3. Garber K. Ready or not: personal tumour profiling tests take off. J Natl Cancer Inst. 2011; 103(2): 84-6.
  4. Gilden K. Personal medicine & genomic profiling enter the mainstream? Direct-to-physician marketing. Austin, Texas: The Oncology Group. Available from:  Accessed: 2nd February 2015.

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