Clinical proteomics firm SomaLogic this week published results from a 1,326-subject trial applying its aptamer-based Somamer technology to the discovery of protein biomarkers for the early detection of lung cancer.
The study, published in PLoS One, identified 44 candidate biomarkers, from which the researchers built a 12-protein panel that, according to the paper, was able to distinguish cases of non-small cell lung cancer from controls with 89 percent sensitivity and 83 percent specificity. The results from the study were initially published in Nature Precedings in June.
SomaLogic is now acquiring samples for validation trials of the 12-marker panel that it hopes to finish by the middle of next year, clinical research director Rachel Ostroff told ProteoMonitor. It's also putting together a pair of prospective studies – one in-house and one with samples from collaborators including the National Cancer Institute – comprising several hundred lung cancer cases and roughly 1,000 controls that it plans to launch this spring.
SomaLogic has partnered with Quest Diagnostics to commercialize the lung cancer diagnostic, with a laboratory-developed version of the test slated for launch next year and a US Food and Drug Administration-approved version planned for 2012.
The company continues to refine the 12-marker panel, Ostroff said, using its technology to "look at those 12 proteins plus a number from that [initial] list of 44."
It's also working to transition the assay from a large-scale microarray format to a smaller plate-based version more suitable for clinical settings. In particular, it is exploring the use of read-out methods including microarray-based hybridization, Luminex bead-based nucleic acid quantification, and real-time quantitative PCR.
The lung cancer panel is aimed primarily at two applications, director of corporate strategy Mark Messenbaugh told ProteoMonitor – as a general early screening test for identifying high-risk patients in need of further work-up to test for the disease, and as an aid in determining whether lung nodules detected during imaging procedures are cancerous.
Currently, pulmonologists have no good way to determine whether such nodules are malignant, he said. "[Doctors] are seeing spots, and depending on the size of the spot, nine out of 10 or 19 out of 20 aren't cancerous, but they can't tell which are the 10th or 20th in those numbers."
Current best practice, Messenbaugh said, consists of "watchful waiting where they send you home and tell you, 'Come back in three months and I'll tell you if it grew inside you.' There's a real risk that it will grow and metastasize over the interim, and so over and over again [doctors] have told us they wish we could help solve this problem."
Doctors are faced with the decision to either watch a "nodule to see if it's growing and looks like it has the characteristics of cancer, which involves perhaps letting an early cancer evolve into a late-stage cancer which is very difficult to treat," or performing a biopsy on a possibly benign growth "with the risks that go with biopsies and other invasive procedures," Ostroff said. "A non-invasive blood test to help sort out those issues is something our pulmonologist colleagues have told us they are certainly looking for."
"There's a very big need for this," William Rom, professor of medicine and environmental medicine at the NYU School of Medicine and a collaborator on the study, told ProteoMonitor. "A test to guide the workup of a nodule identified by a CT scan would really be helpful."
He cautioned, however, that while the test performed well in the PLoS One study, it remains to be seen how it will perform in a prospective trial following patients with lung nodules.
"The study that they reported was a case control study looking at lung cancers compared to smoker controls, and their marker worked very well for that kind of study," he said. "We don't know if their marker will work on nodules. That's what needs to be done in a future validation study."
Collection of samples for such prospective trials has been made easier by the fact that differential diagnoses of lung nodules is such a widely acknowledged problem, Messenbaugh said.
"True positives in a study you can confirm with a biopsy, but with true negatives the test of trueness is time. You have to see that any nodule in a person's lungs doesn't grow over one or two years," he said. By using previously collected longitudinal samples, SomaLogic hopes to speed up that process.
"There are a lot of folks who have been doing this type of study in the context of CT screening, x-ray screening," Messenbaugh said, noting that University of Pittsburgh researcher Jill Siegfried has longitudinal samples from more than 3,000 people from a CT screen study that the company hopes to use. "Admittedly, it's retrospectively designed, but using prospectively collected samples. We think it replicates best practice but does so in a way that collapses time."
The 12 proteins in the current version of SomaLogic's lung cancer diagnostic are cadherin-1, CD30 ligand, endostatin, HSP90α, LRIG3, MIP-4, plietrophin, PPKCI, RGM-C, SCF-sR, sL-selectin, and YES. They were identified using the company's Somamer detection platform, a system of modified aptamers – single-stranded nucleic acids – capable of detecting proteins in blood at sub-picomolar concentrations.
The company has promoted Somamers as an alternative to antibodies for protein discovery and identification, saying they offer a high level of specificity that allows for multiplexing at a significantly larger scale than is possible using traditional ELISA platforms. While ELISAs typically have an upper multiplexing limit of around 20 to 30 analytes, Somalogic has been running Somamer-based arrays capable of multiplexing 850 analytes and aims to have assays capable of measuring 5,000 proteins simultaneously within the next several years.
In September it signed a collaboration agreement with Emerald BioStructures to investigate the structural and binding features of its aptamers with the aim of improving their specificity (PM 09/10/2010).
The company has also launched validation trials for protein-biomarker based pancreatic cancer and mesotheliama diagnostics developed on the Somamer platform. Quest has the rights to the pancreatic cancer panel, while the company is still exploring commercialization strategies including possible partnerships for the mesotheliama test (PM 10/15/2010).
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