Revolutionary Liquid Biopsies Can Find the Cells that Matter Most

A cancer research company's "No Cell Left Behind" technology can identify just five cells in a sample of 30 million.

by Cassie Kelly
August 28, 2017

Cancer is notoriously sneaky. But, for more than 1.5 million new patients a year, there might finally be a way to detect and treat this devastating disease before it’s too late.

At Epic Sciences, a company devoted to cancer research, a team of multidisciplinary scientists is working tirelessly on a method that identifies cancer in a revolutionary way: liquid biopsies. To understand this new method, it is important to understand how traditional cancer screening and research takes place.

Cancer is first identified with a blood test that screens for abnormal cells using a pre-fabricated sorting method. Once it is confirmed that a person has cancerous cells, doctors then perform a biopsy by removing a tissue sample from the affected area and testing it for malignant cells. Biopsies are often uncomfortable, even painful, and can lead to infection of the area, like  pneumothorax. Possibly the biggest hurdle for a patient facing metastatic cancer—cancer that has spread to the blood or lymph system—is that repeating biopsies becomes increasingly challenging for a number of reasons. The area may have scar tissue making it difficult to take a another sample, or  spread to other parts of the body, or there may be multiple types of cancer within one tumor, which makes treatment especially tricky.

“The reality is that metastatic disease is very heterogenic,” Ryan Dittamore, Vice President of Translational Research and Clinical Affairs at Epic Sciences, said. “If you have 100 cancer cells and 90 are the same and 10 are not, and you treat the 90, those ten are going to just keep growing. Or maybe you’ve targeted all of them but some cell has developed a resistance mechanism to that drug and it starts proliferating. This means we need to look at the cells, not just DNA, to understand the complexity of metastatic disease.”

Epic Sciences liquid biopsy method scraps everything we understand about cancer screening and starts from the beginning. Instead of testing the tissue DNA, they test the blood. So, no incisions are made, just a quick blood draw. From there, they look for a very specific type of cell called a circulating tumor cell (CTCs). This type of cell is a key indicator of metastasis because it can travel from the site of the tumor, through the bloodstream, and seed new growths throughout the body. By scanning for CTCs, Epic Sciences is able to pinpoint exactly what are cancer cells and what are not.

Finding Five Cancer Cells in a Sample of 30 Million

The No Cell Left Behind computing program by Epic Sciences uses a series of algorithms and machine learning to characterize every single cell in a blood sample. It starts with spreading the cells onto a series of slides, which are stained with a protein marker to identify the nucleus of the cell, making them easily identifiable. The program is not designed to sort on a large-scale basis like traditional machines, instead it sifts through each individual cell, rapidly categorizing them with extreme precision. It is able to see just five abnormal cells in a sample of more than 30 million.

“They used to say, ‘I can’t look at millions and millions of cells, I need to preselect for a certain type of cell and only capture that,’” Dittamore explains. “But biologically, we started to understand how diseases recur and we recognized that the cells can take on very different structures as you treat because the disease is biologically evolving, so it makes sense that their physical shape and size will change as well too.”

Because the technology only needs a blood sample, a patient’s cancer can be monitored on a routine basis. This allows for a constant, real-time stream of information about the disease’s progression.

“We have a playground of different artifacts on the slides that we can identify cancer in this movie kind of way rather than taking a snapshot of what the tumor was a week ago, month ago, or year ago,” Dittamore said. “Every week or month we can get a blood draw and see how the immune system is changing to better manage treatment for patients. With this technology, we can extend lives dramatically just by identifying what is the right drug for the right patient at the right time.”

No Cell Left Behind Discoveries

The team has already made groundbreaking discoveries about different forms of metastatic cancer. In November 2016, Epic Sciences published findings on the biomarker AR-V7, which is linked to metastatic prostate cancer, in the journal European Urology. The technology was able to successfully identify the marker, making it the first predictive test for prostate cancer.

Another significant discovery was published in the journal of the American Association of Cancer Research on April 26, which revealed findings on the biomarker PD-L1, which was believed to be a potential predictor of how a patient might respond to immunotherapy. Using the No Cell Left Behind technology, the scientists found that CTCs could identify PD-L1 and indicate malignant tumors. This new method avoids the risks of an invasive biopsy or even unnecessary surgery and delivers a more concrete answer on a patient’s chance of survival with the help of immunotherapy drugs.

“Only a small fraction of patients have dramatic responses to immunotherapy,” Dittamore said. “Then there’s another 20 or 30 percent of patients who receive minimal benefit and about half who receive none at all. These drugs are very expensive and it’s a huge economic burden on cancer patients and their insurers. So, our goal was to find a way to precisely identify a patient’s chance of survival.”

The Future of Liquid Biopsies

Other companies are also working on liquid biopsy technology are OncoCyte and Grail, which are focused on early detection of cancer, and Guardant, which is focused on interesting mutations that may detect cancer.

“We are focusing on patients who have been diagnosed because over half our cancer care dollars go in the metastatic space and there is major inefficiency in treatment,” Dittamore said. “As an industry, we are moving the needle, but not as much as we need to.”

The 2017 budget for cancer care is slated at just over $5.3 billion, according to the National Cancer Institute, which also received an additional $300 million for the Cancer Moonshot Initiative, set up by former Vice President Joe Biden. One program funded by the initiative is the Blood Profiling Atlas pilot, which brings together nonprofits, academic groups, and industry leaders like Epic Sciences to create a vast database of results from liquid biopsies that will help accelerate their development and get them on the market.

For now, the team at Epic Sciences is intensely focused on metastatic cancer, however, Dittamore envisions a bright future for the technology.

“The program has applicability to anything rare in the blood,” he said. “That is true for identifying autoimmune disease, for non-invasive prenatal testing, and even for cardiac disease. There is a whole world of possibilities and we expect we are just scratching the surface.”

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