Liquid Biopsies for Circulating Tumor Cells: A New Prognostic Tool?

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While liquid biopsies could prove successful in monitoring treatments, these tests might also find early-stage cancers that, left alone, would never progress.
While liquid biopsies could prove successful in monitoring treatments, these tests might also find early-stage cancers that, left alone, would never progress.

Advances in next-generation sequencing (NGS) are allowing researchers to scour the blood for new clues to tumors' unrelenting complexity. Using ‘liquid biopsies,'” these tests measure DNA snippets and other genetic materials tumors shed in the blood for signs of molecular changes that may signal worsening disease.

Although the technology is not new, experts say, the improved sensitivity of NGS holds enormous promise for guiding cancer treatments in the future, and perhaps unmasking early cancers long before symptoms appear. Many agree, however, that early uses will likely involve pairing these blood-based tests with traditional tissue biopsies, the current standard, until further clinical studies are done.

“The application side of all new technologies often lags behind,” said Leonard Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society in Atlanta, Georgia. Not only does it take time to prove efficacy, he said, but with liquid biopsies scientists must sort out the “signal from the noise” — distinguishing between tiny fragments of circulating tumor DNA in the blood and a sea of floating DNA shed by normal healthy cells.

Still, much like checkpoint inhibitors, liquid biopsies have attracted intense research interest in the past several years. Dozens of studies were presented on the topic at the American Association for Cancer Research and American Society of Clinical Oncology meetings earlier this year.

Several approaches are being used.1 One measures intact circulating tumors cells. Other tests, considered furthest along, measure tumor-related DNA. A third option looks for exosomes, a grab bag of genetic debris, including DNA, RNA, and metabolites found in the blood.

Outpacing several competitors, Roche scored a big win in June, 2016, with the US Food and Drug Administration (FDA)'s first approval of a liquid biopsy test as a companion diagnostic for advanced non–small cell lung cancer.2 It's the only test the agency has approved so far.

The Roche liquid biopsy test detects mutations in EGFR on the surface of cells, found in an estimated 10% to 20% of patients with NSCLC. The blood test is expected to particularly benefit patients who may be too ill or otherwise unable to undergo a tissue sample biopsy.

The comparative ease of liquid biopsies over tissue sampling is just one of its obvious appeals, experts say. Other advantages include a potentially smaller expense and an ability to repeat blood draws over time to track cancer progression, said Nancy Davidson, MD, vice president and director of the Fred Hutchinson Clinical Research Division in Seattle, Washington. “Circulating tumor markers can show you the entire tumor —not just a single metastasis that you're biopsying,” she said.

That capability, according to Dr Davidson, may enable physicians to stay a step ahead of evolving cancers.

The initial use of liquid biopsies may, however, be mixed, with most early tests looking for specific mutations, such as EGFR, that respond well to known targeted drugs. But, eventually, other molecular targets may arise, allowing for new ways to attack tumors and hopefully improve patient outcomes.

As for testing in healthy people with no known cancer, Davidson demurred: “there's a lot of work to do, but I don't rule it out.”

In advanced disease, researchers already know how useful liquid biopsy can be, especially in tumors with a lot of mutations, according to Maximilian Diehn, MD, PhD, assistant professor of radiation oncology at the Stanford University School of Medicine in Palo Alto, California. Dr Diehn, who specializes in lung cancer, said many studies show concordance or agreement between tissue biopsy results and those seen in liquid biopsies in advanced cancers, when DNA concentration and tumor burden are high.

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