Medicine’s New Stethoscope

Detecting cancers with a blood test sounds simple enough, but is it just hype or are liquid biopsies here to stay?

AsianScientist (Aug. 10, 2017) – When 33-year-old Natasha Stork experienced stomach pains in August 2015, she wasn’t overly concerned. After all, she’d just had her first baby six weeks ago, and figured some post pregnancy aches were normal. But when the pain became unbearable, Stork’s worried husband rushed her to the closest emergency room in Melbourne, Australia.

There, doctors delivered devastating news. Stork had tumors throughout her body—in her stomach, liver, hip bones and bowel. Immediate treatment was imperative, but doctors first had to determine what kind of cancer she had. Doing a biopsy would take too long—Stork couldn’t wait two to three weeks for the results to begin her treatment. So her doctors decided on a different tack: to run a blood test.

The premise was simple: collect a small amount of blood and screen it for fragments of DNA that cancer cells tend to shed when they’re metastasizing. Liquid biopsy, as the test is known, has generated immense interest in recent years because it holds the potential to revolutionize the way cancer and other diseases are diagnosed.

It’s an industry that is forecasted to grow up to 25 percent in the next five years, reaching a value of US$1.66 billion by 2021. Liquid biopsies could be a game changer, so much so that Eric Topol, a professor of genomics at the Scripps Research Institute in San Diego, predicted it will become the “stethoscope for the next 200 years.”


Speed and specificity

Topol’s prediction may be bold, but it’s certainly not unfounded. Compared to traditional biopsies, liquid biopsies are relatively painless, non-invasive and have a much quicker turnaround time. Stork, for instance, had to wait just six hours to find out she had stage four melanoma.

“Liquid biopsies ideally reduce medical costs and risks of expensive and invasive biopsies,” Dr. Tan Min-Han, CEO, founder and medical director of cancer diagnostics company Lucence Diagnostics, told Asian Scientist Magazine. “As a medical oncologist familiar with real-world bedside care, I foresee that better diagnostics will allow for improved care for my patients.”

Importantly, liquid biopsies help address a problem that plagues traditional biopsies: that tumors are heterogenous.

“With tissue biopsies, depending on where you get the cells from, you might get very different results,” said National University of Singapore’s Professor Lim Chwee Teck, whose startup Clearbridge mFluidics has developed a cell-capturing chip and the accompanying technology to analyze the single cells captured.

Liquid biopsies circumvent that problem by employing technology that traps cancer cells coursing through the patient’s blood. “In liquid biopsies you are actually capturing the cells that are undergoing metastasis—those are the important cells you want to analyze,” Lim said.



Moving medicine forward

When Stork’s doctors received her liquid biopsy test results, they didn’t just learn what kind of cancer she had, but also the particular mutation that caused it. Armed with that knowledge, they placed Stork on treatment tailored explicitly to her condition, targeting the BRAF mutation. The results were remarkable: within six weeks, a further biopsy and a follow-up CT scan showed that her blood was now completely free of tumor DNA.

Besides targeted therapies that interfere directly with the root cause of cancer, doctors can also continuously monitor patients as they progress through treatment.

“The key value proposition for liquid biopsies is that you can have real-time feedback, unlike tumor biopsies which are usually done just once or twice,” said Lim.

Other experts are a bit more wary.

“I have no problem with liquid biopsies as a test for following tumor response to treatment; the issue is whether it’s an appropriate test for screening,” said surgical oncologist Dr. David Gorski, medical director at the Barbara Ann Karmanos Cancer Institute in Detroit.

“A liquid biopsy is basically just a blood test, so it has all the same problems in terms of potential for over-diagnosis and a lack of specificity,” Gorski explained to Asian Scientist Magazine.



Going mainstream

Liquid biopsies, it seems, aren’t necessarily the panacea for cancer detection. While some cancers—like breast, lung and prostate—spread through the blood, others make use of the lymphatic system.

In addition, while most cancer types release a significant amount of DNA into plasma, there might be some cancers that release only a few cells, said Professor Dennis Lo, who teaches medicine and chemical pathology at the Chinese University of Hong Kong. “For example, brain or pancreas cancer might be particularly difficult to detect.”

There’s also another barrier in the way of liquid biopsies moving to the forefront of cancer diagnosis. “Assuming the blood test is positive, you still have to say, ‘Where is the cancer likely to be?’” said Lo, who won the 2016 Future Science Prize for his role in developing non-invasive prenatal testing. “Such tissue-of origin technology is still ultra-new.”

It’s an issue that Lo’s company Cirina is tackling. The San Francisco-based firm has developed a technique to pinpoint the origin of a plasma DNA fragment, by studying its specific methylation pattern.

“Data is king.
It will show if liquid biopsy is the way to go.”

Researchers also need to conduct further clinical trials to determine how sensitive the new technique is and which cancers it can detect. To date, the largest liquid biopsy trial, conducted by the California based company Guardant Health, has involved more than 15,000 patients. Lo has an even larger trial in the works—studying 20,000 men in Hong Kong for nasopharyngeal cancer—that is due to finish soon.

“Data is king,” said Lim. “It will show if liquid biopsy is the way to go.”



This article was first published in the July 2017 print version of Asian Scientist Magazine. Click here to subscribe to Asian Scientist Magazine in print.

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Copyright: Asian Scientist Magazine.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Sandy holds a BSc in life sciences, and masters degrees in both forensic science and journalism.

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