By Doug Macron
Asuragen this week announced that it has signed a deal to work with the Translational Genomics Research Institute to develop a test to detect pancreatic cancer using blood-based microRNAs as biomarkers.
The move marks the company's first effort to develop an miRNA screen in a clinical setting.
Under the terms of the arrangement, Asuragen and TGen will study blood samples collected from healthy individuals and from patients with pancreatic abnormalities and pancreatic cancer, all of which will be obtained from TGen's Pancreatic Cancer Biospecimens Repository, the partners said.
Other cancer samples will come from a collection developed by the Pancreatic Cancer Research Team, a group of international pancreatic cancer investigators that are led in part by TGen.
Specific details of the arrangement, including commercial terms, were not disclosed.
Since it was spun out of Ambion in 2006 (RNAi News 1/12/2006), Asuragen has primarily been focused on miRNA-based diagnostics. In 2008, it became the first company to introduce such a product when it began marketing a test designed to differentiate pancreatitis from pancreatic ductal adenocarcinoma in resected pancreatic specimens (RNAi News 4/24/2008).
The company is also currently working on developing a similar test based on fine-needle aspirate samples (RNAi News 2/4/2010).
Looking to leverage the research it has already conducted in pancreatic disease, as well as years of work on the analysis of miRNAs in biological fluids, the company has now expanded its focus beyond diagnostics to include screening tests, which generally must be minimally invasive in order to ensure their adoption.
According to Bernard Andruss, director of collaborations and business development at Asuragen, the company has "for quite some time … been doing a lot of work in-house to understand the best procedures for isolating and detecting microRNAs in biofluids, including blood, serum, and plasma, and working out the technical details of how to do the analysis.
"We've done the internal feasibility work and felt we were ready to move into a clinically oriented project and sample set," he said. And because Asuragen could partner with TGen, which will provide access to well-annotated samples and analysis tools, as well as a "world-class" research team, "we really felt that this was a good project."
Asuragen isn't alone in seeing the potential in tests that use blood-based miRNAs, but developing such products has thus far proven a significant challenge.
In early 2009, Rosetta Genomics announced that it would shift its focus away from its core miRNA diagnostics efforts onto screens. At the time, the company said its first such product, a test to detect colon cancer, could hit the market by the end of that year.
Rosetta later backtracked on that timeline, and at the end of 2009 said it had scaled back its miRNA screen programs and would once again turn its attention to diagnostics after running into significant "technical obstacles" (RNAi News 12/31/2009).
Indeed, effective isolation and analysis of miRNAs in biological fluids holds a number of challenges, according to one key figure in the field. University of Massachusetts Medical School investigator and miRNA pioneer Victor Ambros told RNAi News last year that the phenomenon of miRNAs in circulation remains "mysterious," and their meaning "still pretty obscure."
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"There are hundreds of them that can be detected in human plasma," he said. "It's just not clear what they represent. A portion of those could represent debris from cells that are being turned over in one part of the body … and being taken through the circulation to be filtered out through the liver or kidney.
"The field is at the very early stages," Ambros added.
Andruss conceded that there are technical challenges that face any kind of screening test, such as the increased impact of "even a small number of false positives or false negatives … when you are screening a broad population." But he noted that "there are reasons to believe that microRNAs may be particularly good markers for use in circulating biofluids, particularly the fact that they appear to be relatively protected from degradation."
When developing screens, there is the need to "design your experiments [to control] for as many variables as possible so that the markers you discover and take forward into validation have a reasonable chance of being verified and validated in further clinical studies," he said. The collaboration with TGen gives Asuragen "access to the tools and right sample sets and good [sample] annotation to really address those questions."
Andruss declined to provide a timeline for when the pancreatic cancer screen might be commercially available, noting that "we're fairly early on in the process."
Still, he said, Asuragen's development of the pancreatic ductal adenocarcinoma diagnostic and "other feasibility work" has provided the company with some promising miRNA biomarker candidates "that we would look to go forward with. … But we are also doing some parallel discovery [research] on this project … [because] we don't want to leave any stone unturned in trying to come up with the best performing markers we can."
Meanwhile, Asuragen continues to move forward with other miRNA programs. In addition to the FNA version of its pancreatic cancer diagnostic, the company has "other projects internally around microRNAs for a variety of other diseases," namely colon cancer, Andruss said.
"We have presented … some work that we've done, in particular, looking at the recurrence risk in colon cancer, [which is] promising work we're moving forward," he said. "We have also been working in a variety of other solid tumors in collaboration with various groups, but those [efforts] are either at earlier stages or ones that we're just not publicly commenting on at this point."