Top FAQs with cancer researchers
Our recent webinar—featuring two scientists working at the forefront of cancer research—focused on liquid biopsy approaches using circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) to explore the potential of early diagnosis, patient stratification for targeted therapies, and minimal residual disease (MRD) monitoring in lung cancer and glioblastoma.
Dr. Atocha Romero, Head of the Liquid Biopsy Laboratory at the Hospital Puerta de Hierro in Madrid, spoke about the possible clinical utility of liquid biopsy in lung cancer management. She discussed how ctDNA could potentially recapitulate the molecular information on different tumor lesions and help identify oncogenic mutations underlying treatment failure. In non-small cell lung cancer (NSCLC), detecting actionable mutations through ctDNA profiling can guide the investigation of targeted therapy. Dr. Romero also demonstrated how the levels of ctDNA correlate with survival outcomes in NSCLC.
As early adopters of the QuantStudio™ Absolute Q™ Digital PCR System, Dr. Romero’s lab harnesses the power of digital PCR to accurately quantify ultra-rare variants in ctDNA for non-invasive biomarker analysis.
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Dr. Inmaculada Ibáñez de Cáceres, Director of Experimental Therapies and New Biomarkers in Cancer Group and Head of the Cancer Epigenetics Laboratory at INGEMM in Madrid, discussed advancements in liquid biopsy for DNA epigenetic profiling in glioblastoma and its potential clinical implications. Due to the sensitivity challenges of using circulating cell-free DNA (cfDNA), the team pivoted to using EVs, especially exosomes, for their ability to bypass the blood-brain barrier and preserve DNA integrity.
Her team pioneered a new quantitative assay called dp_qMSP (double-probe quantitative methylation-specific PCR) that offers higher sensitivity than standard MSP in detecting MGMT methylation, a key clinical biomarker in glioblastoma. This method proved effective in both tissue biopsies and EVs extracted from liquid biopsies. The team is currently working toward standardizing digital PCR to achieve greater sensitivity in these measurements.
Here are some key questions that were answered during the webinar. This Q&A provides insights into the current state and future directions of liquid biopsy in cancer research, reflecting the expertise and perspectives of Dr. Romero and Dr. Cáceres.
How critical is the sensitivity of technology in analyzing liquid biopsy samples, for example, from lung cancer samples?
Dr. Romero emphasized the necessity to maximize sensitivity in liquid biopsy technologies. Although liquid biopsy accelerates biomarker testing and can potentially help stratify patients for targeted investigational therapies, limitations arise due to small plasma volumes and low circulating-free DNA yields. She stressed the need to communicate the sensitivity limitations and the risk of false positives and perform additional tests with tissue biopsies whenever possible.
What factors influence the ideal sensitivity in liquid biopsy?
Dr. Cáceres highlighted that ideal sensitivity depends on the clinical research context—are the results exploring diagnosis, prognosis, treatment response, or minimal residual disease? Sensitivity also varies with the technique used for liquid biopsy. For research purposes, ideal sensitivity would depend on research goals, biomarker types, sample characteristics, and technology used.
What distinguishes cfDNA from ctDNA?
cfDNA and ctDNA are molecularly similar. ctDNA originates from the tumor and, therefore, is differentiated by its oncogenic mutations, while cfDNA includes all circulating DNA fragments.
How useful is ctDNA for potential early cancer detection?
Dr. Romero is optimistic about using liquid biopsy analysis of ctDNA in exploring early lung cancer detection and screening and possibly combining it with imaging to develop more effective screening programs. She also mentioned the utility of measuring analytes apart from ctDNA, such as proteins, microRNAs, and non-genetic features of DNA, such as methylation patterns and topologies.
What volume of sample is typically used for ctDNA testing, and how does it affect sensitivity?
The higher the volume of blood/plasma, the higher the DNA yield, which in turn enhances the sensitivity of the tests. The recommended minimum is 4 mL of plasma, but larger volumes are preferred for better sensitivity. The difficulty lies in the low percentage of tumor DNA in blood, which is often less than 0.1%.
How do digital PCR (dPCR) and next-generation sequencing (NGS) complement each other in translational cancer research?
Both technologies are seen as complementary, and the choice usually depends on various factors, including the research goal, sensitivity requirement, and cost. Digital PCR is useful for high-sensitivity detection of known markers, while NGS provides broader information and can uncover novel markers. Integrating both may advance research on early cancer detection, screening, and personalized medicine.
Where do you see the liquid biopsy evolving in the next five years?
Dr. Romero foresees significant advancements in clinical research on liquid biopsy for early-stage cancer screening, minimal residual disease monitoring. She anticipates highly sensitive assays becoming instrumental in lung cancer research.
Dr. Cáceres predicts advancements toward single-cell analysis and multiomics in liquid biopsy, which is currently limited to tissues. This higher sensitivity may enable single-cell transcriptomics for potential diagnosis and personalized medicine.
Did you miss the live webinar? Watch it on-demand today
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