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With a market opportunity in the billions (as much as $20 billion by some estimates), diagnostic companies are rushing the liquid biopsy floodgates with new tests designed to make finding and monitoring cancer as easy as a blood draw or urine sample.

The true clinical impact of this technology remains to be seen and there are some early limitations of these tests that will need to be addressed, but some doctors say liquid biopsies could really transform cancer treatment. To validate the power of blood- and urine-based cancer tests, several of the key players in the space presented data at the recent American Association for Cancer Research (AACR) meeting in New Orleans.

Tissue biopsies will continue to be the gold standard approach to diagnosing cancer for at least the next couple of years, oncologist Samuel Klempner told Medical Device Daily, but the sensitivity of some of these liquid-based technologies should not be underestimated. He said the technology is likely to first play a role in how oncologists monitor disease progression and treatment-response early on, especially in rare cancer cases. Klempner, director of precision medicine at the Angeles Clinic and Research Institute who is affiliated with Cedars-Sinai Medical Center, presented a case study at AACR in which he treated a patient with a BRAF-MEK inhibitor for a rare type of colorectal cancer and used Trovagene Inc.'s urine-based Precision Cancer Monitoring (PCM) technology to confirm the presence of the BRAF V600E mutation and then monitor the response to treatment in advance of imaging tests. Klempner also described the case in a report published in Cancer Discovery.

Klempner said a tissue biopsy detected the presence of the BRAF mutation and that there are drugs targeting that pathway but this particular form of cancer is not a studied disease indication for those drugs so he was not sure if the BRAF-MEK inhibitor would work against that tumor.

"We were looking for ways to assess whether or not our therapy was working," he said.

Imaging technology such as CT can be used to monitor a patient's response to a therapy, but it doesn't always show evidence of a response early enough. Klempner also noted that there are no blood-based biomarkers for neuroendocrine tumors so Trovagene's urine-based technology offered an ideal solution. The test was able to show the patient responding to the treatment long before any changes could be assessed with imaging technology, he said.

Because this was a one-patient study, Klempner said more rigorous data will need to be collected, ideally in a clinical trial, but so far it seems that the test should play a role in monitoring early disease response, especially in rare cancer cases.

By using a urine-based test rather than a blood-based test, Klempner said his patient benefited from a convenience advantage that he hadn't given much thought to before the study. She has to drive 45 minutes for office visits, which she would have had to do more frequently if he had used a blood-based technology instead of the urine-based test.

Trovagene, of San Diego, said this patient case study shows that as more therapies are designed to target and inhibit specific mutations that are associated with cancer growth, cancers could potentially be treated according to the genomic profile of the tumor, rather than tumor location alone. This is especially important for less common tumor types with limited treatment options, the company said. Trovagene offers both urine- and blood-based BRAF, KRAS and EGFR oncogene mutation assays.

Mark Erlander, chief scientific officer of Trovagene, said the case study provides a good example of how a disease can be classified and treated based on genomic information. "We believe this is the way cancer will be treated in the future," he said.

The combination BRAF-MEK inhibitor therapy is undergoing clinical investigation across multiple tumor types and the information provided by Trovagene's test can be helpful in demonstrating that the treatment regimen is having its intended effect, Klempner said.

There are some limitations of current liquid biopsy technologies that will keep tissue biopsies as the gold standard, at least for a while, Klempner said.

"Tissue allows us to assess multiple genes at the same time whereas most of these blood and urine tests assess one gene at a time," he said. If there are 10 drugs available that might work, it is important to assess all 10 of those target genes and then, after starting treatment, liquid biopsies can be used to monitor its effectiveness.

Another limitation that liquid biopsy companies face, Klempner said, is penetration into the broader oncology market. Overcoming that barrier is a matter of educating the smaller community practitioners about the availability of these tests and how they can be used to improve patient outcomes.

Out for Blood

Vortex Biosciences Inc. also presented data at AACR to support the ability of its technology to rapidly collect highly enriched populations of circulating tumor cells (CTCs), undamaged by labels or reagents, for colorectal and prostate cancer research. Previous research demonstrated the performance of Vortex's technology in isolating CTCs in breast and lung cancer research.

Vortex, of Menlo Park, Calif., has developed a fully automated benchtop system called the Vtx-1 for collecting intact CTCs using microfluidic technology. Inside the Vtx-1 chip, unlabeled CTCs in whole blood are trapped in microsale vortices while smaller red and white blood cells pass through. After selective trapping into the microfluidic chambers, CTCs can be flushed and collected into a variety of containers for downstream analysis, the company said.

The ability of the technology to isolate CTCs and ctDNA without killing the cells in the process is important, particularly for personalized medicine applications, Dino Di Carlo, a bioengineering professor at the University of California at Los Angeles and an advisor to Vortex, told MDD.

CTC enrichment technologies have been limited by complex sample processing, poor scalability, low sample purity, reliance on cell surface proteins for isolation and dilute output volumes that require additional cell concentration steps, according to the company.

Gene Walther, CEO of Vortex, told MDD that the technology could potentially help scientists advance cancer research and accelerate the development of new diagnostics and therapeutics.

Lung Cancer: An Interesting Application for Liquid Biopsy

Another study added validation to Berlin-based Epigenomics AG's panel of blood-based DNA methylation biomarkers for the detection of lung cancer. The FDA recently approved Epigenomics' Epi Procolon liquid biopsy test. (See Medical Device Daily, April 14, 2016.)

Epigenomics CEO Thomas Taapken told MDD that lung cancer is the second area of focus for the company now that it has FDA approval for its colorectal cancer test.

"To develop blood-based tests for cancer is a very important task and while there are many companies working on this, there are not so many out there that have been doing this on the basis of a proprietary set of biomarkers and that is maybe the biggest differentiating factor we have," he said. "What we have is a platform that allows us to go after several cancerous diseases without having to enter what could become a commodity market."

In lung cancer, the company has not yet done any major clinical studies and the data presented at AACR is considered validation research that was completed on about 116 patients, some healthy patients, some with lung cancer and some with non-malignant tumors.

Lung cancer is an interesting application for liquid biopsy, Taapken said, because of the new U.S. recommendation to screen high risk patients (those with a long history of smoking) annually with low-dose CT scans starting at age 50.

The problem with that screening method, he said, is that it uses radiation and also results in a high percentage of false positives. Low-dose CT typically produces positive results about 27 percent of the time and not all of those cases are true positives, he said.

"You cannot have millions of people screened and then have every third patient undergo a tissue biopsy," Taapken said. "That is where liquid biopsy tests come into play. We are trying to develop a test that will help those positively tested patients after low-dose CT screening to confirm or rule out the presence of lung cancer."

If the liquid biopsy confirms the low-dose CT positive, the patient would then be referred for a tissue biopsy.

Editor’s Note: This is the first of a two-part series from Thomson Reuters’ daily med-tech news service, Medical Device Daily, exploring both the business opportunities and the clinical potential of liquid biopsy. Watch for the second story in the series coming soon here on State of Innovation.