Liquid Biopsies
Liquid biopsy approaches, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and plasma proteomics, provide a minimally invasive window into tumor dynamics and have the potential to capture real-time information on ADC efficacy.
Liquid biopsies take advantage of the fact that tumors continuously release cells, DNA fragments, and proteins into the bloodstream. By analyzing circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and protein profiles in blood samples, researchers can obtain a real-time, comprehensive picture of the tumor’s biological activity. This minimally invasive approach complements traditional tissue biopsies, enables repeated monitoring over time, and can reveal treatment response or emerging resistance earlier than conventional imaging. While CTCs can be studied to assess how cancer cells react to specific drugs and ctDNA reflects the genetic evolution of the tumor, proteomic analyses provide insight into functional processes such as tumor signaling, immune responses, and treatment-related toxicity. Together, these technologies offer a dynamic and integrated view of how each patient’s cancer behaves and responds to therapy.
How does it work?
CTC
CellSearch: a reference technology for counting tumor cells
The CellSearch system is a reference technology approved by the U.S. Food and Drug Administration (FDA) for detecting and counting circulating tumor cells in blood samples. It operates in a semi-automated manner and identifies tumor cells based on specific markers on their surface.
After the cells are identified and counted using fluorescent markers, their genetic material can be extracted and analyzed. This allows researchers to study DNA methylation changes, which provide important information about tumor behavior and response to treatment.
EF-FACS: analyzing tumor cells one by one
The EF-FACS method, developed by Gustave Roussy, makes it possible to isolate and analyze circulating tumor cells (CTCs) found in the blood. Unlike conventional approaches, it does not require any prior enrichment step, allowing a higher number of tumor cells to be recovered.
Using a highly sensitive flow cytometry technique, cells are sorted individually, enabling precise detection of proteins targeted by specific cancer treatments such as antibody–drug conjugates (ADCs). Each cell is then analyzed at the molecular level, providing valuable insight into tumor diversity and how cancer cells change over the course of treatment.
Proteomics
PEA (Proximity Extension Assay) technology has revolutionized protein analysis by enabling highly specific and sensitive detection of proteins in complex biological samples. Unlike traditional methods, PEA allows for simultaneous analysis of hundreds of proteins with minimal sample volume, significantly improving the speed and depth of proteomic research. Its unique antibody-based approach ensures high accuracy, even in low-abundance proteins, making it a game-changer in identifying biomarkers and understanding disease mechanisms at a molecular level.
ctDNA
Circulating tumor DNA (ctDNA) is small fragments of tumor-derived DNA that can be detected in the blood. In the OASIS program, ctDNA analysis provides a minimally invasive way to monitor the disease over time.
By analyzing ctDNA, OASIS aims to better understand tumor genetics, track molecular changes during treatment, and detect early signs of response or resistance to antibody–drug conjugates (ADCs). This approach complements tissue-based analyses and helps capture tumor heterogeneity that may not be visible from a single biopsy. Overall, ctDNA contributes to a more dynamic and personalized assessment of cancer, supporting the development of optimized and more effective treatment strategies within OASIS.