While traditional tissue biopsies provide critical information to diagnose and treat cancer, surgery to obtain biopsies can be painful, invasive, and even unsafe for patients, depending on the location of the tumor. The recent Biotech Connector speaker series brought together three investigators to present innovations in a different type of biopsy: the liquid biopsy.
Liquid biopsies are usually blood tests that detect circulating tumor DNA (ctDNA), DNA fragments that tumor cells shed into the bloodstream. Recent advancements are making liquid biopsies an increasingly useful tool for both patient care and research.
Minimal residual disease
“Liquid biopsies have the potential to detect, characterize, and monitor cancers earlier than is possible with our current conventional approaches,” said Kaitlin Victor from Labcorp Oncology.
In particular, Victor said that liquid biopsies can detect disease recurrence earlier than standard imaging or clinical presentation. She presented a highly sensitive assay that captures minimal residual disease (MRD), which is a small number of cancer cells remaining after treatment.
Victor shared that a study in stage III colon cancer patients found a positive ctDNA status post-surgery was associated with a higher risk of cancer recurrence and a shorter time to recurrence than for patients with a negative ctDNA status.
She concluded that ctDNA MRD detection following cancer treatment is predictive of relapse, and it could be used to identify participants who would benefit from adjuvant therapy (additional therapy given alongside the primary therapy) and assess response to treatment.
Personalized medicine
Amanda Peach of the Frederick National Laboratory’s Molecular Characterization Laboratory (MoCha) presented a retrospective analysis of the NCI-MATCH (Molecular Analysis for Therapy Choice) study that compared assay results from tumor biopsies and ctDNA.
NCI-MATCH was one of the largest precision medicine platform trials sponsored by NCI. Participants were assigned to receive different therapies based on the genetic changes found in their tumors.
For this comparative study, MoCha investigated about 2,200 participants with rare and uncommon tumors who had provided both a tissue and blood sample. The goal was to assess the reliability of MoCha’s liquid biopsy assay by comparing it to the tissue assay. They found that 85.5% of the oncogenic mutations observed in the tissue were also identified in the ctDNA.
Peach suggested that, given this alignment, liquid biopsies “could potentially be used for patient screening or stratification in future NCI-sponsored precision medicine trials.”
Improving clinical trials
Lorenzo Rinaldi, Ph.D., of Delfi Diagnostics discussed the potential for liquid biopsies to improve clinical trials.
“Around 70% of Phase II trials do not advance,” he said.
He suggested that monitoring the molecular response via liquid biopsies during Phase I studies could improve Phase II success rates via early response detection.
However, he said existing assays—which typically monitor mutant allele fraction (MAF), a measure of the percentage of mutant alleles within all alleles in the sample—are expensive.
He presented what is said is a more cost-effective method that uses tumor fraction, which is the level of ctDNA in a liquid biopsy sample. Specimens with higher tumor fraction have more ctDNA. He showed that both methods similarly predicted survival outcomes in a study of patients with metastatic colorectal cancer and in metastatic lung cancer cases. Another study showed that the tumor fraction method detected molecular response earlier than traditional imaging methods.
Join us on November 20
The Biotech Connector will return on November 20, 2025, to tackle the topic of cell therapy. Attend in-person at the Advanced Research Technology Facility in Frederick, Md, or join virtually. The event—which is jointly hosted by the Frederick National Laboratory and Frederick County Chamber of Commerce—is free to attend, but registration is required.
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