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Marrying Pathology with Single Cell Genomics to Predict Cancer

July 2019  One of the keys to diagnosing and treating cancer is understanding the disease on the single cell level. Quite often, damaged cells can be poised on the cliff, uncertain whether to become malignant or take a more benign path.

That same uncertainty afflicts medicine. For example, everybody gets heartburn, but many people experience a more severe variety, called gastroesophageal reflux disease (GERD). Over time, GERD’s acid damage can alter esophageal tissue, leading to Barrett’s esophagus.

Here’s where it gets tricky. Around three million people have Barrett’s esophagus, but only a small number will develop esophageal cancer: Around 18,000, according to the American Cancer Society. Of those, around 12,000 will develop esophageal adenocarcinoma caused by GERD. 

But we don’t know which patients are at higher risk, and that puts physicians in an uncomfortable position. Should they put patients through a series of invasive endoscopies and pinch biopsies or play the favorable odds, knowing they might miss a deadly cancer?

“There's peer-reviewed literature that questions both the efficacy and cost effectiveness of all this screening,” says Illumina Ventures Partner, Tom Willis. “It's just crying out for a precision medicine tool to better pinpoint the patients that are most at risk.”

That’s the approach that’s driving Illumina Ventures portfolio company Cernostics, which is combining traditional pathology with single cell genomics to predict which Barrett’s esophagus patients are most likely to develop esophageal cancer.

Something Old, Something New

For the most part, pathologists assess Barrett’s patients the old-fashioned way: They look at esophageal cells through a microscope to identify structural changes. This approach can be quite subjective and produces uncertain returns.


The Cernostics assay, called TissueCypher, retains this structural approach but layers on protein diagnostics to identify markers that, in certain combinations, can indicate a patient is more likely to get cancer.


“If we can understand where one or more protein markers are expressed within the cells, or if they’re co-expressing more than one biomarker within a cell, that's biologically meaningful,” says Cernostics CEO, Mike Hoerres. “This marriage of multiplexed biomarker detection in the context of tissue architecture within biopsies provides great predictive power. Our software tools give us the ability to understand what's happening at the cellular and tissue level – think 20th century pathology meets 21st century artificial intelligence.”


The test gives physicians and patients better options. In some cases, if a patient is at higher risk, problem cells can be destroyed. While this technology has been around for a while, physicians have never been able to identify the people who would most benefit.


Other patients may simply need to be monitored, for example, getting an endoscopy every five years or so. Right now, many patients return sooner because they’re concerned something will slip through the cracks. A low risk index from TissueCypher could be reassuring.


“For too long, patients have had to wonder whether their Barrett’s would cross over into cancer, and we’ve never really had good answers for them,” says Willis. “That’s a real payoff for precision medicine tools like TissueCypher; they can take away some of that worry.”


At the recent Digestive Disease Week conference in San Diego, Cernostics produced new research validating TissueCypher’s predictive abilities, generating quite a buzz at the GI conference. Kenneth Wang, a leading gastroenterologist from Mayo Clinic, highlighted TissueCypher during a presentation.


Cernostics processes the tests in their CLIA reference laboratory, based in Pittsburgh, the company’s hometown. Gastroenterologists from anywhere in the U.S. can order the test and send tissue sections from their esophageal biopsies. Meanwhile, the company is continuing to

validate TissueCypher with larger studies and is actively reaching out to the medical community to increase acceptance.


“We want gastroenterologists to know about our data, read the papers and start to get familiar with how TissueCypher could impact their patients,” says Hoerres. “This is a test that can really impact decision-making.”

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