Liquid biopsy: a blood test to diagnose lung cancer

Scientific and Medical Context

Non-small cell lung cancer (NSCLC), accounting for approximately 80% of lung cancers, is one of the leading causes of cancer mortality. Its often late diagnosis makes therapeutic management complex. Precise molecular diagnosis is essential to guide patients toward the most effective personalized treatments.

Traditionally, molecular analysis relies on invasive tissue sampling. In recent years, liquid biopsy, which analyzes circulating tumor DNA (ctDNA) directly from a simple blood sample, has emerged as an innovative, minimally invasive alternative that allows for dynamic and regular patient monitoring.

IHU RespirERA, through the Laboratory of Clinical and Experimental Pathology (LPCE) at Nice University Hospital, possesses world-renowned expertise in the field of liquid biopsies and cutting-edge molecular sequencing.

Project Objectives

This ambitious project aims to evaluate, optimize, and integrate the use of liquid biopsy into the diagnostic and therapeutic pathway of NSCLC patients. Specifically, it aims to:

• Compare the performance of various innovative sequencing panels in liquid biopsy versus standard tissue biopsy analyses.
• Identify key somatic oncogenic alterations at initial diagnosis or during disease progression.
• Validate the clinical utility of large sequencing panels capable of detecting complex alterations, such as gene fusions and copy number variations, which are difficult to identify using traditional approaches.
• Discover and validate new diagnostic and prognostic markers (methylation, clonal hematopoiesis, ctDNA).

Methodology

Retrospective and prospective cohort:

• Patients with advanced NSCLC, with blood (liquid biopsy) and tissue samples available at initial diagnosis and, for some, at disease progression.

Evaluated Sequencing Strategies

• PCR-based targeted sequencing (AmpliSeq).
• Hybrid capture-based targeted sequencing (Hybrid Capture).

Innovative Panels Tested

• SOPHiA Genetics: MSK-Access Panel.
• Hedera Dx: HP2 Hedera Panel.
• Agilent: Avida Panel.
• Roche: Avenio Expanded Panel.
• ThermoFisher Scientific: Oncomine Precision Assay, Genexus platform.
• AstraZeneca / BioSciences Pillar: OncoReveal Core and Fusion Panels.
• Illumina: NextSeq550Dx and NextSeq2000.

Strategic Collaboration

• Côte d’Azur Biobank, the first biobank specialized in thoracic pathology accredited in France.
• Industrial and academic partnerships with world leaders in molecular sequencing (SOPHiA Genetics, Agilent, Roche, ThermoFisher, Illumina, AstraZeneca).

Expected Results and Clinical Impacts

• Identification of the optimal liquid biopsy panel for daily clinical use, ensuring precise and reliable molecular diagnosis.
• Improvement of patient quality of life through non-invasive, easily repeatable sampling, reducing the distress associated with invasive biopsies.
• Better patient stratification, allowing for targeted therapeutic management from initial diagnosis or in case of progression.
• Facilitated access to clinical trials, thanks to the complete molecular profiling of the cancer via liquid biopsies.

Long-term Perspectives

This project is fully aligned with the ambition of IHU RespirERA, which places technological and molecular innovation at the heart of personalized lung cancer care. By promoting the widespread adoption of liquid biopsies in daily clinical practice, it paves the way for truly individualized and predictive pulmonary medicine. Furthermore, this study addresses a crucial challenge: the effective management and in-depth analysis of massive data generated by high-throughput sequencing to better understand the genomic complexity of lung cancer and improve its diagnosis and treatment.