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Time for Reality Check: Clinical Proteomics Not There Yet, According to HUPO Panel

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SEOUL ­– While proteomics has made progress during the past few years, significant challenges remain and the idea of bringing the field to the clinical level remains a far-off goal, according to speakers at a panel discussion at the Human Proteome Organization’s annual conference here this week.
 
While there is plenty of proteomics-based researching being conducted worldwide, to date, few proteomics-based products have had any clinical relevance, leaving many to wonder where the field is headed and what can be done to accelerate the process to bring proteomics-based diagnostics to the clinical setting.
 
The panelists speaking this week did their best to convey their optimism about what has been achieved so far, but also acknowledged that many major hurdles continue to dog proteomics research.
 
In particular, the search for protein biomarkers of clinical utility has bogged down, according to the panel. Even while there are plenty of studies being conducted to find biomarkers for cancer, neurodegenerative diseases, heart disease, and an assortment of other ailments, many of these studies are of negligible value, said members of the panel.
 
“The field of biomarkers is like the Wild West,” said Samir Hanash of the Fred Hutchinson Cancer Research Center and the founding president of HUPO. “It’s really chaotic.” The majority of those doing biomarker research, he said, are actually ill-equipped to do the work due to limited funding and other resources, and the result is sloppy science.
 
Henry Rodriguez, director of Clinical Proteomic Technologies for Cancer at the National Cancer Institute, said that the protein biomarker field is rife with issues. For one thing, laboratories have been unable to reproduce experimental data – both their own data, as well as those of other labs.
 
The “enormous” diversity, range, and dynamics of proteins also pose their own challenges, as does the lack of standardization and protocols, he said. Finally, he cited a lack of adequate biospecimens and clinical data.
 
Sudhir Srivastava, chief of the Biomarkers Research Group in NCI’s Division of Cancer Prevention, added to that list, noting that there is too much variation in samples; the sheer magnitude of the proteome is overwhelming; and many studies are poorly designed and include biases.
 
Indeed, the panel repeatedly stressed the importance of the human factor over technology in pushing proteomics ahead. Several panelists said that current technology allows researchers to do what they should be doing, but even the best technology will not compensate for improper workflows.
 
“The problem isn’t the technology,” said Jan Schnitzer, scientific director at the Sidney Kimmel Cancer Center. “The problem is in the questions we ask of technology.”
 
While standardization is one of the key buzzwords in proteomics, some members of the panel said that instead of standards, rigorous, well-designed, well-characterized studies are what the field needs.
 
“Proteomics is an observational science,” said Martin McIntosh of Fred Hutchinson’s public health sciences division. “People need to understand the [demands] of designing a rigorous experiment. They’re not doing experimental science in the true sense.”
 
However, Hanash acknowledged that the paucity of biomarker-based diagnostics that have reached the US Food and Drug Administration for possible approval is not unique to proteomics. No scientific discipline has been able to unravel the mystery of bringing biomarkers from discovery to market, he said.
 
According to Hanash, proteomics has made notable progress in the past few years. Just five years ago, for example, a team of researchers was able to identify 502 proteins in human plasma, using 2.5 liters of plasma.
 

“The field of biomarkers is like the Wild West.”

In 2003, HUPO set up the Human Plasma Proteome Project with the goal of identifying 5,000 proteins in plasma. By the end of 2004, the project had identified 889 proteins with high confidence. And last year, with improvements in technology, that figure jumped up to more than 6,000 culled from less than 10 milliliters of plasma.
 
“In five years, we have gone from 500 proteins to more than 6,000 proteins. That is phenomenal,” Hanash said.
 
And there have been other signs of progress, he said. An in-depth characterization of cell proteomes can be achieved now. Researchers also can interrogate thousands of recombinant proteins in an array format. And tools have been developed for analysis of the glycoproteome.
 
Still, the business community has not embraced proteomics, and some in the pharmaceutical industry say that firms are continuing to either scale back their proteomics operations or shutting them down completely because they are not seeing returns on their investments.
 
Srivastava from the NCI said that he believes that proteomics has value to the investment community, but at the moment, there is still no clear business model for commercializing proteomics discoveries as a clinical or diagnostic tool. As a result, investors are not sure who the purchasers of such products will be.
 
The time is approaching when the field will need to develop some clinical applications in order to “show the world [proteomics] has some commercial potential,” he said.
 
In the next five years, according to Hanash, steps needed to accelerate clinical proteomics include rallying support among the movers and shakers of the field and identifying unmet needs such as resources and technologies. He also pushed for greater sharing of data, a barrier that is slowly coming down.
 
At another panel discussion, Mike Snyder, a professor of molecular, cellular, and developmental biology at Yale University, called the sharing of data in proteomics “pretty pitiful compared to other communities.” In genomics research, for instance, researchers readily and willingly disclose their raw data with their peers, he said.
 
Hanash also that proteomics needs to define milestones so that progress can then be definitively measured and recognized by those outside the field. Without such milestones, he said, the success stories in proteomics is difficult to tell.
 
“It seems to me this is something we have to make some adjustments for,” he said.

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