At the American Association for Cancer Research's annual meeting this month, Celera presented data on a protein biomarker diagnostic for lung cancer, drawing attention to the company's proteomics program after several years of keeping it largely in the background.
The panel, which is aimed at detecting lung cancer in non-smokers, consists of six protein markers, and in a study examining 40 cases and 40 controls, it was able to distinguish between benign and malignant lesions with a sensitivity and specificity of 83 percent.
According to Charles Birse, associate director of product development at Celera, the likeliest use for the test is as an assay for evaluating suspicious lesions picked up during CT scans. Such scans, he said, are likely to become a more common technique, particularly in light of recently released results from the National Lung Screening Trial – a National Cancer Institute study involving more than 53,000 current and former heavy smokers – that found that CT scans reduced lung cancer mortality by 20 percent compared to standard chest X-rays.
The NLST results are "likely to prompt some form of nationwide screening," Birse told ProteoMonitor. "If that does get implemented then there's going to be a major need for a test that can distinguish the status of pulmonary nodules" detected during CT scans.
Such a test, Birse noted, would likely require specificity in the 90- to 95-percent range and sensitivity around 70 percent to be diagnostically useful. At that level of specificity the panel currently shows sensitivity in the 60 percent to 70 percent range, he said.
To discover the markers, the Celera researchers analyzed 13 tissue samples and 17 cell lines for differential protein expression using an Applied Biosystems QSTAR XL mass spectrometer. They focused on cell surface and secreted proteins, Birse said, under the assumption that these would be the easiest markers to pick up in serum.
From more than 500 potential biomarkers identified during discovery, they selected the six comprising the current panel, generating ELISAs for these proteins that they then ran on 600 serum samples to develop and validate their diagnostic algorithm. They then ran this validated test on the 80 cases and controls, generating the data presented this month at AACR.
The test is aimed at non-small cell lung cancer, which makes up roughly 85 percent of lung cancer cases, Birse said, adding that the markers have performed well "across the major histochemical [tumor] cell types" as well "as across the four stages of cancer," making the researchers "fairly confident that we're seeing good performance across the major groupings."
Additional studies are needed, however, to confirm these initials results, said Sudhir Srivastava, head of the Cancer Biomarkers Research Group at the National Cancer Institute's Early Detection Research Network.
"At this point in time, [the test] isn't ready for prime time," he told ProteoMonitor, saying that the panel needs to be tested in larger patient cohorts. He also suggested that the panel be tested against longitudinally collected samples "to see how far they can detect [lung cancer] before it becomes clinically evident."
According to Birse, Celera may this summer participate in a study sponsored by the EDRN and headed by Harvey Pass – director of the division of thoracic surgery and thoracic oncology at New York University's Langone Medical Center – that will allow it to test the panel on roughly 300 cases and controls.
The company's participation could be affected by its impending acquisition by Quest Diagnostics, Srivastava said, noting that "the future participation of Celera in our EDRN project is currently in limbo because Celera has been bought out by Quest Diagnostics."
However, if the study goes forward as originally planned it will run Celera's diagnostic plus a proteomics-based lung cancer test from biotech firm Somalogic and a DNA methylation-based test from a team of Johns Hopkins researchers on the same 300 samples, comparing the results generated by the different platforms.
"All the samples are going to be completely blinded… and all the samples are associated with a pulmonary nodule, and the group at NYU has the information on the workup on those nodules," Birse said. He noted that Celera expects "to be able to articulate more on future R&D activities once the transaction with Quest has been completed."
The proposed Quest acquisition, which was announced on March 18 (GWDN 03/18/2011) and this week cleared US antitrust review (GWDN 04/13/2011), could help move development of the test forward, however.
Although he declined to comment on the Quest deal directly, Celera vice president for corporate affairs David Speechly told ProteoMonitor that the company has "been looking at partnering this effort with another party that has greater competence and capability with running clinical trials or running clinical work in a lung cancer setting."
Quest's strategy, he said, "is to drive proprietary diagnostic tests with greater differentiation, and so the strength of our discovery [research] is something that they find highly attractive."
Currently, Quest's $671 million offer for the company is set to expire on April 25 at 5:00 pm Eastern Standard Time. Since the deal was announced, Celera investors including activist hedge fund business Starboard Value & Opportunity Fund have pressed the company to renegotiate a better price. Furthermore, several investors, including the New Orleans Employees Retirement System, have filed lawsuits alleging that the management team has breached its fiduciary duty by agreeing to the sale at a price that undervalues the company (GWDN 04/07/2011).
Although Celera is best known for its genomics research, the firm was conducting proteomics discovery work on a number of different cancers before it spun out from parent company Applera in 2008, Speechly said.
After the split, though, "we had a strong focus on moving the business toward profitability," he said. "Within [proteomics] we really focused on the programs that had the most momentum and the highest likelihood of success – of which lung cancer was the leading one. That doesn't mean that we stopped all the other [proteomics] work. Just that it's on the back burner."
As the Quest acquisition "moves through, opportunity [will] come to light as to how these programs will be researched and funded," Speechly said. For the moment, however, the company's proteomics focus remains squarely on the lung cancer diagnostic, he noted.
He declined to give a timeline for commercialization of the test, but noted that work on it "is still early stage."
According to Birse, the researchers are currently putting together a manuscript detailing the discovery and preliminary validation work that they plan to submit for publication in "the very near future."
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