Almac Diagnostics has moved closer to launching its microarray-based test for stage II colorectal cancer recurrence and plans to debut it in the US sometime next year.
A study published last week in the Journal of Clinical Oncology detailed how researchers discovered the gene signature underlying the ColDx test, which the company claims can be used to identify patients with a higher risk of disease recurrence within five years following surgery.
Almac said it believes the data in the paper, authored by researchers at Almac and Queen's University Belfast, could enable oncologists to make better treatment decisions.
Austin Tanney, scientific liaison officer for the Craigavon, UK-based firm, told BioArray News that the test, manufactured by Affymetrix in its cartridge GeneChip format, will initially be available via a US Clinical Laboratory Improvement Amendment-compliant facility. He added it will be co-marketed with an undisclosed "US-based diagnostics company."
Of all Almac's planned diagnostics — it is also researching breast, lung, and ovarian cancer tests — ColDx is the closest to commercialization. The firm, a division of Northern Ireland's Almac Group, has been developing the assay for years. In March, Tanney said Almac had hoped to market the test in 2012, and that it was "entering its final stage of validation" (BAN 3/15/2011).
As described in the JCO study, Almac used its internally developed Colorectal Cancer Disease Specific Array, also manufactured by Affy, to analyze 215 samples from 14 different centers. The samples were composed of a "balanced set of good- and poor-prognosis patients," Tanney said.
Based on that work, Almac's bioinformatics team derived a 634-gene-signature associated with stage II colorectal cancer recurrence. They validated the signature by applying the classifier to an independent group of 144 patient samples, which yielded a hazard ratio of 2.52, Tanney said.
"Importantly, the signature is able to predict not just recurrence of the disease within five years but also survival," he added.
As noted in the JCO paper, all of the samples surveyed were from formalin-fixed, paraffin-embedded tissues. Tanney said that the ability to derive signatures from these samples will give the test a "huge advantage" in the market.
"Our Cancer DSA and Xcel array platforms have been designed and optimized to work with FFPE samples," said Tanney. "We also have many years of experience working with [FFPE samples] and have developed a great deal of expertise in extracting good quality data from these samples."
In the paper, Almac's scientists noted that formalin-fixation degrades mRNA transcripts through the cross linking of RNA to protein. Most of this degradation occurs immediately, but some transcripts continue to degrade with time, they reported.
To overcome this, they designed probe sets to target the 3' end of mRNAs to "enhance the ability to detect degraded transcripts."
The 'Best Platform'?
According to the National Cancer Institute, colorectal cancer is the third most diagnosed cancer in the US, averaging about 101,000 cases per year. The most common treatment for the disease is surgery to excise malignant tissue.
However, in a statement last week Almac said surgery is effective in only around 80 percent of patients and the remaining 20 percent will experience a recurrence. Moreover, these patients may benefit from adjuvant chemotherapy, which NCI advises as a treatment protocol only in stage III cancer cases.
Almac is positioning ColDx as an adjuvant itself to current prognostic markers, including T-staging, which shows how far the primary tumor has grown into the wall of the intestine; and grade, which determines "how closely the cancer looks like normal colorectal tissue when seen under a microscope," according to the American Cancer Society.
Tanney said both methods are "weak," arguing that they have hazard ratios of around 1.5 or less, while Almac's test's is 2.53. This means that those patients with the identified signature are more than twice as likely as the control population to experience disease recurrence.
Additionally, Almac noted in the paper that ColDx's signature "does not require individual interpretation [by lab techs or physicians] and may offer a more standardized approach than conventional histopathologic factors."
Tanney also credited the firm's use of microarrays both to identify ColDx's signature and as the basis for the diagnostic.
"Without the use of a microarray platform, a signature like this could not have been discovered as we were able to take an unbiased transcriptome-based approach to discovering the signature," said Tanney. "The correct delivery platform for a diagnostic is dependent on many variables. In this case, with a gene signature of over 600 genes, an array is currently the best platform."
ColDx will compete with Genomic Health's Oncotype Dx Colon Cancer Assay, a 12-gene real time-quantitative PCR-based diagnostic designed to predict recurrence in stage II colorectal cancer. Genomic Health launched the assay, performed at its CLIA lab, last year and published a validation study in JCO earlier this month.
Without explicitly mentioning the Oncotype Dx assay, Almac's scientists took aim at the test in their JCO paper, arguing that arrays "can measure several thousand mRNA transcripts at once and may be able to capture the complex biology that underlies colon cancer recurrence better than single gene markers."
Almac is now planning a further retrospective validation of ColDx in a large cohort of stage II colon cancer samples collected as part of a clinical trial.
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