Webinar: Introduction to Liquid Biopsies for Precision Oncology

Webinar summary

In this webinar, Dr. Simon Heeke, Assistant Professor at MD Anderson Cancer Center and lead of the Liquid Biopsy Translational Working Group, presents an overview of liquid biopsy applications in precision oncology, with a focus on treatment selection and longitudinal monitoring in advanced-stage cancer.

The presentation explores how circulating tumor-derived nucleic acids, including circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA), can provide real-time insights into tumor biology using minimally invasive sampling approaches.

Study overview

Liquid biopsy approaches are designed to complement or, in some contexts, replace more invasive tissue-based sampling methods by analyzing tumor-derived material released into body fluids. The presentation focuses primarily on blood-based liquid biopsy applications in oncology, although the broader applicability of liquid biopsy technologies across multiple disease areas is also acknowledged.

Tumor-derived material enters circulation through both passive processes, such as apoptosis and necrosis, and active biological release mechanisms, including extracellular vesicle secretion. These processes generate detectable ctDNA and ctRNA signals that can be interrogated using molecular profiling technologies.

The webinar highlights the utility of ctDNA and ctRNA for:

• Detection of actionable genomic alterations
• Identification of gene rearrangements and fusion events
• Longitudinal monitoring during therapy
• Prognostic assessment
• Rapid molecular profiling workflows

The presentation also examines integrated DNA/RNA sequencing approaches, comparisons across liquid biopsy platforms, and the use of alternative liquid biopsy sample types to improve molecular testing turnaround times and expand access to precision oncology.

Key findings

ctDNA and ctRNA enable complementary molecular profiling

• ctDNA supports detection of mutations, copy number alterations, epigenetic modifications, and chromosomal rearrangements.
• ctRNA enables assessment of gene expression and enhances detection of fusion transcripts due to removal of intronic regions during RNA splicing.
• Integrated DNA/RNA analysis improves characterization of clinically relevant gene rearrangements.

RNA-based analysis improves fusion detection

• RNA sequencing approaches demonstrated high accuracy for detection of clinically relevant gene fusions.
• ctRNA-based liquid biopsy approaches successfully identified ALK rearrangements in plasma samples.
• Combined DNA and RNA liquid biopsy analysis increased fusion detection sensitivity relative to single-modality approaches.

Integrated liquid biopsy approaches help improve detection coverage

• Certain gene fusions were detected exclusively through ctDNA analysis, while others were only detected through ctRNA analysis.
• These findings support the use of integrated liquid biopsy workflows combining both nucleic acid sources.
• Detection of fusion events through liquid biopsy was also associated with prognostic insights in longitudinal analyses.

Liquid biopsy supports longitudinal treatment monitoring

• Serial liquid biopsy sampling enables tracking of variant allele frequencies during therapy.
• Changes in ctDNA levels may reflect treatment response, persistence of tumor-associated signals, or emergence of resistance-associated alterations.
• Longitudinal molecular monitoring may support future strategies for treatment adaptation and resistance detection.

Clinical trial applications demonstrate feasibility

• In the RAMOSE trial evaluating osimertinib with or without ramucirumab in EGFR-mutant non-small cell lung cancer, liquid biopsy demonstrated robust detection of EGFR alterations across treatment arms.
• Detection remained feasible even in patients with brain metastases, a setting often associated with reduced ctDNA shedding.

Cross-platform concordance supports reliability

• Variant allele frequency measurements across multiple liquid biopsy platforms showed strong correlation independent of sequencing methodology.
• Concordance was observed across amplicon-based, hybrid capture-based, and integrated sequencing workflows.

Liquid biopsy improves turnaround time and accessibility

• Compared with tissue biopsy workflows, liquid biopsy approaches significantly reduce pre-analytical delays associated with tissue acquisition and processing.
• Blood-based workflows streamline access to sequencing-ready nucleic acids and reduce overall time from sample request to molecular report generation.

Alternative sample sources expand molecular profiling opportunities

• Fine needle aspirate supernatants and cerebrospinal fluid demonstrated feasibility as liquid biopsy substrates for rapid molecular profiling.
• These approaches achieved strong concordance with tissue-based analyses while improving access to molecular data.

Liquid biopsy may expand access to precision oncology

• Liquid biopsy sampling requires less specialized infrastructure compared with tissue biopsy procedures.
• The presentation highlights the potential for liquid biopsy to improve access to molecular testing in regions with limited oncology resources or reduced access to specialized centers.

This webinar demonstrates that liquid biopsy technologies provide a minimally invasive framework for real-time molecular characterization in precision oncology. Integrated analysis of ctDNA and ctRNA enables improved detection of actionable genomic alterations, particularly gene rearrangements, while supporting longitudinal monitoring during therapy.

The findings further emphasize the analytical reliability of liquid biopsy platforms, the utility of multimodal sequencing strategies, and the potential for rapid, accessible molecular profiling workflows using alternative biofluid sources. Collectively, these advances position liquid biopsy as an increasingly important tool for translational research and molecular testing in precision oncology.

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