Diagnostics

Liquid biopsy highlights from #ASCO2017

Running low on talking points for your liquid biopsy watercooler chats? Fear not. An education session at ASCO 2017 highlighted some of the latest findings from the field — and we have a recap of that recap here.

Blood

Liquid biopsies were – unsurprisingly – a hot topic for discussion at the 2017 American Society of Clinical Oncology (ASCO) annual meeting, held in Chicago from June 2-5.

A proper smorgasbord of posters and abstracts were on display. For the main course, approximately 1,500 attendees packed into one of the auditoriums for a joint ASCO-American Association for Cancer Research (AACR) education session about progress in the field.

Here are some highlights from their analyses.

Young at heart. While the concept of circulating cell-free DNA dates back to the 1940s,  the term “liquid biopsy” was first coined in a 2010 paper published in the journal Trends in Molecular Medicine.

Blood is where it’s at. If they had to pick one — and they did have to pick one, for time reasons — the panelists would choose blood-based liquid biopsies as the immediate future of the field. Other bodily fluids, such as saliva and sputum, are several steps behind and likely don’t offer the same breadth of diagnostic potential.

Look for CTCs and ctDNA. Within blood, the experts singled out circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) as the most advanced and readily applicable markers. Again, there are many more molecules to explore, including immune cells and miRNA. At least one company is even looking for patterns across multiple markers, identified through the use of machine learning. But that’s a longer play.

For ctDNA, it matters when you take the blood sample. Maximilian Diehn of the Stanford Cancer Institute noted that ctDNA has a half-life of around 30 minutes. “So you’re really looking at what has been released within the last few hours,” he said. Fortunately, one of the major perks of liquid biopsies is that you can test patients regularly in a minimally invasive way…

Surveillance and testing for “minimal residual disease” is one of the most exciting applications. Just because you can’t see cancer in a scan doesn’t mean it isn’t there. In the future, liquid biopsies could be used to routinely check for any remnants of the disease, or recurrence at its very earliest stages — before any tumor is visible or palpable. The tests could also be used to monitor a patient’s response to a targeted therapy. Is the number of CTCs in the bloodstream falling? If not, what else can we do?

CTCs can cross the blood-brain barrier. As Klaus Pantel of the University Medical Center Hamburg-Eppendorf eloquently put it; “The blood-brain barrier is no Berlin Wall for these tumor cells.” Up until 2014, the scientific consensus was that tumor cells couldn’t cross from the brain into the blood. It turns out they can. It was an important discovery, not least because brain cancers can be particularly hard to biopsy using traditional tissue collection methods.

Liquid biopsies could help doctor’s plan for secondary treatment options. Scientists increasingly recognize that standard tissue biopsies may deliver an incomplete picture, given the heterogeneity of the cells within any one cancer. So if one mutation is identified and targeted, the treatment may miss another important cluster of tumor cells driven by different mutations. By capturing a diverse line-up of cancer cells and DNA fragments, liquid biopsies could help oncologists identify secondary and tertiary mutations to target if the first therapy fails.

As long as the tests are actionable. The catch is that early detection of metastasis doesn’t necessarily help us treat it, said Daniel Hayes, clinical director of the breast oncology program at the University of Michigan Comprehensive Cancer Center. And that’s a critical leap. Patient outcomes need to be improved to justify the tests. Part of that rests on the diagnostics, but a lot is also in the hands of drug developers.

And just because the DNA carries a mutation doesn’t mean that it has been shed from a cancer cell. Another word of warning from Hayes: Healthy tissues also undergo genetic changes. That’s very relevant as we begin earlier cancer screening with liquid biopsies, he said. It’s important not to overreact or to intervene in early-stage cancers that would have resolved on their own.

A formal positioning statement is on the way. ASCO and the College of American Pathologists (CAP) have teamed up to deliver a formal positioning statement, according to Diehn, recognizing the field is now taking giant steps into the unknown. He stressed that it won’t cover practicing guidelines; the organizations instead want to establish standards for things like the scientific validation of the tests.

With few exceptions (two liquid biopsies have thus far been approved by FDA), the tests haven’t yet proven clinical validity and utility, the panelists agreed. There is plenty of optimism, however, particularly in regards to the use of liquid biopsies as a complement to existing diagnostic options.

Photo: MilosJokic, Getty Images 

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