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Protein Arrays: Closer to the Clinic


One of the reasons Lance Liotta and Emanuel Petricoin moved to George Mason University was to pursue translational research through the applied proteomics and applied medicine center. Now they are moving even closer to the clinic with their new company, Theranostics Health.

Making this shift from academic research to the clinic is tricky, but Liotta and Petricoin aim to overcome the snags to bring a proteomics-based, high-throughput technology to the diagnosis and treatment of cancer. Their reverse-phase protein microarray tool measures the activity of proteins in tumor cells — proteins that can be targeted by anticancer drugs. Liotta and Petricoin plan to collaborate with pharmaceutical companies to look at drug targets, and then to bring their tool to pathologists and oncologists to get to the heart of personalized medicine, the patient.

“From the start, our goal was to do translational research. Not just at the clinical end but to start at the basic and go all the way to the clinical for each of the discoveries,” says Liotta. As Petricoin says, “No patient is ever going to benefit by two academic researchers in a university doing something.”

To determine if a patient’s organ or growth is cancerous, doctors commonly perform needle biopsies on an out-patient basis. While less invasive than surgical alternatives, these biopsies only remove a few thousand cells. Though that is enough to tell if the cells are cancerous, it does not give a big enough sample to assess the cells’ proteomic profile. “It’s certainly a quandary because there’s no PCR-like technology for proteins,” says Petricoin. “You’re not going to have an IRB that says, ‘Keep pin-cushioning the patient until you get enough material.’”

In response to this need, Liotta and Petricoin developed a new technology based on reverse-phase protein microarrays. Their printed slide contains immobilized cell lysates and reference standards paired with phospho-specific antibodies to mark their relative abundance, even with a tiny amount of sample. Not only does this technique measure protein levels in the tumor, it gauges whether they are activated. If one protein is active, then downstream proteins in the same cascade may also be turned on — showing that the pathway might be involved in making the cell cancerous. “That’s what we’re interested in because that’s what you’re trying to block with your drug — receptors, the signaling molecules in use,” says Liotta.

But before their tool tells doctors which therapies might benefit a particular patient, Liotta and Petricoin first have to ensure that it meets rigorous standards. By following College of American Pathology and Clinical Laboratory Improvement Act guidelines (they are awaiting accreditation), Liotta and Petricoin try to guarantee the reliability and reproducibility of their tool. In academia, once an experiment works, Liotta says, it is rarely repeated. But when the research has a clinical bent, it needs to be replicable.

As their fledging company gets off the ground, Liotta and Petricoin will partner with pharmaceutical companies to identify phosphoprotein markers that indicate if, and how, a cancer treatment works. Then, to bring the tool to the patient, Liotta and Petricoin will work with pathologists at hospitals to analyze patient tissue. Once a tumor’s activated protein profile is known, oncologists could prescribe a drug that targets that specific pathway. This individually tailored treatment could reduce the long-term after-effects of current cancer treatments. “It’s more than just giving the right drug to the right patient. It’s about withholding the toxic drug from the wrong patient and benefiting quality of life in both directions,” says Liotta. And Liotta and Petricoin think their tool provides that ability.

“Everything seems to be coming together now in the field of individualized therapy,” Liotta says.

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