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The Pathologist / Issues / 2022 / Aug / Liquid Biopsies: Reach for the Stars
Liquid biopsy

Liquid Biopsies: Reach for the Stars

By overcoming the limitations of first-generation liquid biopsies, we can leap light-years ahead in clinical practice

By Dan Norton 08/11/2022 3 min read

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Stargazing and medical research aren’t so different. Both involve peering out into empty space and looking in awe at the breadth and scale of the things going on – things that happen without any of your input. At the same time, it’s incredibly overwhelming. With so much choice, where do you look? Imagine for a moment that every star in the sky is an avenue for medical care being worked on – a method or technique with its own set of pros and cons, successes and failures, advocates and naysayers. Again comes that same question: where do you point your telescope? You can appreciate, and even take joy in, the fact that there’s so much potential for improving patient outcomes – but, at the end of the day, you can only point your telescope at one spot in the “research sky” at a time.

For me, one star burns extra bright in the constellation of cancer diagnostics. When I look across the vast galaxy of projects, developing treatments, and emerging technologies, it’s the shining prospect of liquid biopsies that continues to catch my eye through my telescope.

Tumor-informed liquid biopsies, for those not in the know, can be used throughout the cancer lifecycle. Their use can enable clinicians to manage a patient’s course – from initial diagnosis and biopsy all the way through surgery, therapy, remission, and relapse. These tumor-informed liquid biopsies (TILBs) can show changes in cancer development – both progression and regression – earlier and more accurately than previously possible. TILBs involve first analyzing a patient’s tumor tissue sample using whole genome sequencing, then designing a truly personalized liquid biopsy panel. This “informed” biopsy gives a more comprehensive view of the tumor’s mutational landscape and optimizes sensitivity. After a patient undergoes surgery to remove a tumor, TILBs allow robust calculation of post-surgical survival risk. Specifically, the technique accurately detects molecular residual disease (MRD) at earlier points following surgical resection, meaning that it’s much faster to ascertain whether the tumor was removed entirely or requires further treatment.

Today, most patients who undergo surgical resection of stage II or III cancer are given chemotherapy as a precaution. However, only a small portion of that population benefits from it – and the harsh side effects of chemotherapy on the body are well documented, so eliminating unnecessary treatment would improve patients’ health and quality of life. TILBs can help identify MRD-negative patients who may not require chemotherapy and monitor treatment responses in MRD-positive patients who undergo further treatment by noting changes in tumor load and mutations over time. By leveraging such insights into tumor changes, care teams can adjust therapies accordingly. TILBs can also help determine the efficacy of therapy at a given time point by measuring the level of tumor burden and identifying individual tumor mutations, allowing care teams to tailor treatment on a case-by-case basis.

Beyond treatment, TILBs also have applications for recurrence monitoring. Once a patient is in remission, TILBs can detect tumor signals much earlier than tumor-agnostic liquid biopsies or the current standards of care (including imaging). Such optimized sensitivity enables physicians to provide treatment before the cancer metastasizes, potentially saving and extending lives.

It’s my hope that you are now excited by the TILB-led future that lies ahead of us – and that I’ve inspired you to look beyond your usual patch of the “research sky.” Glance elsewhere and who knows what exciting research could be waiting at the other end of your telescope?

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About the Author(s)

Dan Norton

Associate Director of Product Management at Personalis

More Articles by Dan Norton

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