Liquid biopsy did not begin with sequencing.
It began in 1869, when Thomas Ashworth, an Australian physician, looked through a microscope 🔬 and saw tumor-like cells circulating in the blood of a patient with metastatic cancer.
Today, we know these as circulating tumor cells, or CTCs.
Twenty years later, Stephen Paget gave oncology one of its most powerful ideas: the “seed and soil” hypothesis 🌱🌍
He proposed that metastasis was not random. Cancer cells may travel through the blood, but they grow only when they find the right microenvironment.
In many ways, Ashworth saw the seed.
Paget imagined the soil.
For decades, the field waited for technology to catch up ⏳
That changed when CTC detection became more standardized, especially with the FDA-approved CellSearch® system in 2004.
For the first time, clinicians and researchers had a practical way to capture and enumerate CTCs from blood.
Then, in 2010, Klaus Pantel and Catherine Alix-Panabières gave the field a name that would define a new era: “liquid biopsy.” 💡
Today, liquid biopsy is often used almost interchangeably with circulating tumor DNA, or ctDNA 🧬
But the term was originally coined in the context of CTCs — the idea that blood could provide a noninvasive, real-time window into cancer biology.
As sequencing became faster, cheaper, and more sensitive ⚡
ctDNA moved to the forefront.
It allowed us to:
✔ Detect mutations
✔ Monitor resistance
✔ Assess minimal residual disease
All without repeated tissue biopsies.
But liquid biopsy is bigger than ctDNA.
In 2026, the International Society of Liquid Biopsy (@ISLB) has given the field a broader and more detailed definition 📘 CLICK HERE
🩸 Liquid biopsy now includes the analysis of:
→ Cells
→ Nucleic acids
→ Proteins
→ Metabolites
→ Extracellular vesicles
→ Other molecules released into body fluids
This is an important correction.
Liquid biopsy is not one analyte.
It is not one platform.
It is not only blood.
It's a dynamic way to study disease through accessible body fluids.
The future will be multi-analyte and longitudinal 🔄
CTCs inform us of viable metastatic cells.
ctDNA may reveal genomic evolution.
Extracellular vesicles, proteins, RNA, metabolites, and immune signals may complete the picture.
The next chapter will not be about replacing tissue biopsy entirely.
It will be about asking better questions, earlier:
❓ Is disease still present?
❓ Is resistance emerging?
❓ Is treatment working?
❓ Can relapse be detected before imaging?
From Ashworth’s microscope 🔬
to Paget’s hypothesis 🌱
to Pantel and Alix-Panabières’ 2010 terminology 📖
to ISLB’s 2026 definition
Liquid biopsy has become one of oncology’s most powerful ideas:
A less invasive, more dynamic way to understand cancer as it changes.
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