Diagnostics & Imaging Week

A protein analysis system with a nanofluidic design developed by Cell Biosciences (Palo Alto, California) may forever change the way cancer is diagnosed and allow oncologists to more precisely assess patients' responses to treatment.

"The analogy to use for this technology is PCR [polymerase chain reaction]," Dean Felsher, MD, PhD, associate professor of medicine and of pathology and leader of the Stanford University Molecular Therapeutics Program, told Diagnostics & Imaging Week. "PCR was discovered in the 1980s and now it's commonly used for certain tests. It revolutionized the way we think about measuring DNA and RNA because you didn't need as much material."

He added, "Previously, there was not a way to do this with proteins. Protein analysis will take the same kind of historic course. There will be intense study and validation and gradual incorporation."

Felsher is senior author for a study published in the current issue of Nature Medicine that used the Cell Biosciences device to analyze whether individual cancer-associated proteins were present in the tiny samples and even whether modifications of the proteins varied in response to cancer treatments. Although that study focused on blood cancers, the team is aiming to use the same technique to provide a faster, less-invasive way to track solid tumors.

Just how small of a sample are we talking about? A drop of blood or a piece of tissue that's smaller than the period at the end of this sentence is all that's needed.

The team was originally hoping to be able to develop a proteomic strategy to be applied to clinical specimens.

"The concern has been that when you're trying to study proteomics, the clinical specimens are very precious," Felsher said. "If you're taking care of a patient, you can only get small amounts of material. We wanted to develop a strategy whereby you needed so little material that you could just use a fine needle to aspirate a specimen or blood. When patients get a drug treatment, we could sample a tumor before and after. We would be able to tell whether the drug as working or not."

But a surprise came when the Cell Biosciences technology allowed the researchers to not only measure a protein, but also to monitor changes.

"After we treated a patient, we saw changes in cells in the protein phosphorylation," he said. "We were hoping to find changes, but we were surprised it was so easy to find those novel changes. The test was so powerful and sensitive it allowed us to do an analysis that people wouldn't otherwise be able to do before."

Variations in the way a protein is modified, or phosphorylated, can affect how it functions in tumor progression. Cancer cells often evade common therapies with changing levels of protein expression and degrees of phosphorylation. Being able to analyze repeated small samples from a tumor or blood of somebody undergoing treatment may allow doctors to head off rogue cells at the pass before they have a chance to proliferate.

"We're at the point where now we have a new tool and we need to use it to start looking for these exciting proteomic changes to help examine for diagnostic purposes and therapeutic responses," he said. "Right now it is only an experimental tool because what we're discovering needs to be validated. We're starting to do that. It's very exciting because it can be incorporated relatively easily into clinical studies. We're very eager to get more support to do this. My lab is very well poised to find these novel proteomic changes."

Tim Harkness, president/CEO of Cell Biosciences, told Medical Device Daily, that Felsher's team used a predecessor system of the commercial version called CB1000, just launched this month.

"We're able to see different things using this technology because we can look at very small samples," Harkness said. "Traditional protein analysis requires tens of thousands of cells. With our system, you can use just 25 cells. For the first time, you can take an individual patient's samples and monitor subtle changes in proteins. Our ability to measure those subtle changes is so very important in the diagnosis and curing of a disease."

The commercial version of CB1000 costs $400,000 and is smaller, faster and more robust than the version Felsher uses.

"At some point reference labs would be buyers of this technology when there are validated biomarkers," Harkness said. "Today our focus is on the cancer market and anybody who is broadly interested in cell signaling."

Felsher's team published data based on lymphomas and leukemia. The next step is to apply the process to solid tumors, such as those found in colon or head and neck cancers.

"I suspect the other medical device makers will be very excited about these results," Felsher said. "It's complementary to other technologies. The whole field benefits. The clinical public has been waiting for technology like this that they could easily adopt."

He added, "Mass spectometry allows you to do similar things, but I can't imagine mass spectrometry being readily used in the clinical sphere. It's too complicated. That technology is very expensive. This is much more analogous to PCR. An operator can learn how to use the machine. Eventually it could be adopted so that any lab assistant can use it."

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