By Turna Ray
Celera has validated its mass-spectrometry-based approach for identifying circulating protein biomarkers that detect non-small cell lung cancer at all stages and is currently in the process of deciding whether to commercialize a prognostic assay based on a six- or a nine-protein marker panel.
In collaboration with the New York University Langone Medical Center, Celera recently announced that it had replicated a "novel mass spectrometry-based approach to identify and validate circulating protein biomarkers that detect NSCLC in an independent cohort of individuals with lung cancer."
Celera presented results from early studies in April at the American Association for Cancer Research's annual meeting. Based on results from these studies, Celera said at the time that it was "expediting" commercialization of its mass spectrometry-based lung cancer test.
Celera estimates the test would be launched by 2012. The test would have been launched much later were it not for these promising preliminary results, which allowed the company to move up commercialization plans for the lung cancer test by one or two years [see PGx Reporter 04-22-2009].
According to Celera spokesperson David Speechly, results from the most recent study involving the lung cancer diagnostic confirms the company's "indirect" biomarker discovery approach by looking at lung cancer tissue from surgical resections, lung tumor cell lines, and the medium that the cell lines were grown in.
"Typically, in the detection of markers that are present at higher levels in the serum, one would use mass spectrometry to interrogate the serum itself and compare the results from serum of lung cancer patients with serum from healthy smokers," Speechly told Pharmacogenomics Reporter last week. In contrast, Celera's approach "provides much less complexity for the mass spectrometry analysis."
Celera then confirmed the levels of proteins in lung tissue in patient serum. "Using this approach we demonstrated a significant correlation between those proteins identified from tissues, cell lines, and cell growth medium, and the presence of these proteins in serum from lung cancer patients," Speechly added.
Celera's clinical analyses have resulted in the validation of a nine-biomarker immunoassay on patient samples with Stage I NSCLC, which may be able to detect disease in the earliest stages.
According to a statement from Celera, the nine-biomarker panel assay detected lung cancer with 92 percent sensitivity at 93 percent specificity, and distinguished malignant lung nodules from benign nodules.
In addition, researchers reported promising performance of a six-marker panel derived from the nine-marker panel, which distinguished malignant NSCLC cases with 92 percent sensitivity at 88 percent specificity.
According to Speechly, the company is evaluating the clinical utility of both panels to determine which assay to commercialize.
"We are currently in studies that should help resolve this decision," Speechly said. "The six-marker panel is contained within the nine-marker panel and would provide advantages in terms of the complexity of the assay and associated costs.
"Additional validation studies will determine if the six-marker panel maintains the same level of performance on additional sample sets," he added.
Although Celera did not disclose any novel protein biomarkers in the panel, Speechly mentioned that two previously identified markers, CEA and CYFRA 21.2, are among them.
As the leading cause of cancer mortality in the US, lung cancer caused 29 percent of cancer-related deaths in 2008. In the lung cancer setting, biomarkers are currently not used for detecting disease and there are no screening guidelines for gauging lung cancer risk.
Researchers involved in the development of the assay feel the accuracy demonstrated by Celera’s test shows promise in moving toward a prognostic diagnostic for early lung cancer detection.
"If validated prospectively in other larger cohorts, [Celera’s test] may impact the management of individuals with presumed or diagnosed NSCLC in the future," Harvey Pass, director of thoracic surgery and oncology at the New York University Langone Medical Center, said in a statement.
According to Celera, its nine-biomarker panel could improve detection and diagnosis of lung cancer around various stages of disease. For instance, by combining the assay with CT analysis, doctors can better identify malignant nodules and identify high-risk patients. Additionally, such a panel combined with CT scanning could also be used to better monitor lung cancer progression by enhancing the management of pulmonary nodules.
The panel of nine candidate biomarkers was drawn from a set of 13 biomarkers previously selected from 500 proteins under a proteomic discovery effort.
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The 13 biomarkers were used to test serum specimens using ELISA methods in a preliminary validation set of sera in 103 patients with NSCLC and 104 healthy smokers. Markers that then showed elevated disease expression were validated in an independent collection of serum samples from 39 NSCLC patients, 38 non-smoking individuals, and 20 patients with chronic obstructive pulmonary disease, emphysema or chronic bronchitis, and 20 subjects with ground glass opacity of the lung. This last group will continue to be followed to determine which patients will progress to malignant disease.
"This panel and others described in the study are expected to provide the flexibility to design tests with performance specifications suitable for a variety of diagnostic applications, such as screening individuals at risk for lung cancer and for monitoring of disease following diagnosis and treatment," Celera said in a statement.
Ahead of commercialization, Celera is conducting several validating trials.
Among them, the company is examining the ability of the protein panel to distinguish between malignant nodules and benign nodules in the lung. According to Speechly, although a "significant number" of smokers have been shown to have nodules on radiographic analysis, the large majority of these nodules tend to be benign.
Additionally, the company plans to complete studies confirming the specificity of the panel before launching the test.
"Early results have been encouraging; however we must complete the studies and the analyses of the results," Speechly noted.
In addition to being commercialized as a standalone prognostic test for NSCLC detection, the nine-marker panel may be used in combination with other technologies to monitor disease progression and help guide treatment decisions.
For example, when used following a radiographic imaging test, such as helical CT, the panel "may be able to help physicians make decisions regarding patient workups when a nodule is observed," Speechly said.
Furthermore, the test may help gauge disease recurrence earlier.
"Many times the follow-up requires additional screens at three or six months, for example," Speechly said. "A test positioned here may allow physicians to assess the suspicious-looking nodules and reach a diagnosis earlier."
This panel of nine biomarkers, or "a slightly different panel," has the potential to "help guide therapy," he added.
"While we are reporting the results from a nine-member and six-member panel, we are actually testing 13 markers in the serum of lung cancer patients," Speechly noted. "There may be additional indications where the panel or a variation of the panel may be used such as monitoring for recurrence of disease."
Celera did not disclose its potential commercialization strategy for its NSCLC detection test. However, Speechly noted that the company intends to introduce the test in the US and in international markets.