Panel examines emerging clinical applications of liquid biopsy

While tissue biopsies remain the gold standard of cancer diagnostics, liquid biopsy-based blood analysis has the potential to change clinical practice by providing a new source of information on how to treat individual cancer patients.

Klaus Pantel, MD, PhD
Klaus Pantel, MD, PhD

A panel of researchers discussed the current state of the art, open questions, and potential clinical applications for personalized medicine in this fast-evolving field during the session Liquid Biopsy: From Discovery to Clinical Application. The session was originally presented on Tuesday, April 12, and can be viewed on the virtual platform by registered meeting participants through July 13, 2022.

Klaus Pantel, MD, PhD, from University Medical Center Hamburg-Eppendorf, Germany, served as chair and opened the session with an overview of the potential benefits of liquid biopsy.

“Tissue biopsies are invasive, some locations are difficult to access, and if you access a single metastatic lesion, you may still miss relevant tumor clones and other metastatic lesions,” Pantel said. “The blood is more like a pool of tumor cells and their products that are released from primary or metastatic lesions, including all locations, and this may give you more comprehensive information.”

Another benefit of liquid biopsy blood analysis is that it can be performed serially during therapy, providing real-time monitoring of tumor evolution and therapy response, he said.

“Liquid biopsy can provide clinically relevant information, but the assays need to be harmonized and validated, and we need interventional clinical studies to demonstrate the clinical utility of liquid biopsy,” Pantel said. “The studies are very important because the clinician is not just looking for prognostic relevance, but how the result of the blood analysis changes the treatment of their cancer patient.”

Catherine Alix-Panabières, PhD
Catherine Alix-Panabières, PhD

Catherine Alix-Panabières, PhD, from University Medical Center of Montpellier, France, discussed the biology and clinical relevance of circulating tumor cells (CTCs).

“Even if you have a small tumor but you have more aggressive cells, they have the capacity to be released actively from the primary site into the bloodstream, where they will be attracted by specific organs because of receptors or specific ligands there,” Alix-Panabières explained.

The cells from those distant sites can then be released in the bloodstream, she said.

“With liquid biopsy, you get a pool of cells coming not just from the primary sites, but also from the distant sites that you may not even have known existed,” Alix-Panabières said. “This allows you to really assess the CTC heterogeneity, which is very important and gives you good information [about] the genotype or phenotype of these tumor cells to potentially give precision medicine to these patients.”

Similar to Pantel’s comments, Alix-Panabières emphasized that more interventional studies, algorithms to combine data from different circulating biomarkers, and clear guidelines and standard operating procedures are critical to increasing the widespread use of liquid biopsies.

Victor E. Velculescu, MD, PhD
Victor E. Velculescu, MD, PhD

Victor E. Velculescu, MD, PhD, from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, concluded the presentations with a discussion of the clinical relevance of cell-free DNA fragmentomes for cancer detection and monitoring.

“Genome-wide cell-free DNA fragmentation profiles, or fragmentomes, reflect abnormal packaging and genomic content of cancer genomes,” he said. “Rather than looking at the very limited number of mutations in a targeted panel or a limited number of changes one can find by methylation, if one looks genome-wide, one can actually identify changes in fragmentation patterns across the genome. Analyses of fragmentomes can detect a high fraction of cancers across all stages, providing a new avenue not only for early detection, but for monitoring during therapy and, we hope, intervention.”

Prospective clinical trials of this approach are currently underway for lung and other cancers, Velculescu noted.

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