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Liquid biopsies – new era in cancer diagnosis and monitoring

Liquid biopsy is a test done to analyse cancer markers in blood or other body fluid (such as urine, cerebrospinal fluid, among others). The analysis of these markers, including cancer cells, can bring very important information for early diagnosis, patient monitoring and treatment selection.

In the current medical practice, cancer diagnosis normally relies on the identification of a tumour by clinical imaging. Then, molecular characterization of the tumour is provided by a biopsy of the cancer tissue, which is an invasive and costly process and not always possible, depending on the location of the lesion. Since cancer is a dynamic and heterogeneous disease, liquid biopsy brings the unique opportunity to get updated molecular information at all stages of the disease.

The presence of cancer material in the peripheral circulation of patients was first identified in the 19th century, but it wasn’t until the early Nineties that the technological development allowed to explore these biomarkers to evaluate their significance and clinical potential.

The most popular cancer biomarkers that can be found in peripheral blood and with demonstrated clinical interest, are proteins, circulating tumour cells (CTCs) and circulating tumour DNA. Others, like extracellular vesicles, tumour associated platelets and mRNA fragments are also under active research.

  • Proteins, in specific secreted proteins are soluble molecules secreted by cells that reflect cell state at real time. Abnormal amounts of specific proteins or proteins with (abnormal) modifications that affect cell function and signalling may be biomarkers of cancer. As such, the identification of these alterations in blood samples may be used for patient screening. The number of clinically useful biomarkers that have resulted from this approach is still low. The most common examples are prostate specific antigen (PSA), commonly analysed in the context of prostate cancer, or CA125 a biomarker for ovarian cancer.
  • CTCs are tumour cells that detach from the tumour and travel to other parts of the body through the circulatory system. These cells are fragile in circulation and tend to undergo anoikis (one specific type of cell death). However, some cells acquire resistance and manage to adapt, becoming very aggressive and forming metastasis. Although their role in disease progression has been clearly identified, the main challenge for their routine clinical analysis is that the number of cells can be as low as 1 cell / million mononuclear blood cells. Highly sensitive and accurate techniques are needed to bring the analysis of CTCs to the current clinical practice.
  • Circulating tumour DNA (ctDNA) consists of fragments of genetic material released by cancerous cells. Cell free DNA is continuously released to the circulation by both normal and cancer cells. In 1989 Stroun detected mutated DNA fragments identified as having a tumoural origin. Taking advantage of very well-established molecular biology techniques, as polymerase-chain reaction (PCR) or next generation sequencing (NGS), it is possible to detect very specific mutations from plasma of cancer patients.


Quantification of both CTCs and ctDNA have been correlated with tumour burden and can be used as a marker for disease prognosis and response to treatment.  Also, the molecular analysis of both CTCs and ctDNA can be used to evaluate the presence of therapeutic targets and to design personalised cancer treatments

There are some CTC and ctDNA liquid biopsy tests authorized for clinical use namely in breast, colorectal and prostate cancer (, lung ( and prostate cancer ( There are also recent indications that liquid biopsy analyses can also be used for early detection of cancer.


The synergy of multiple circulating biomarkers will bring specifics of cancer. Combining methods and biomarkers will pave the way for new approaches in cancer management, providing better and personalised care to cancer patients.  The challenge is to develop tools that are efficient and sensitive and to make these tools accessible to all, avoiding high costs or logistic barriers.

In this context, the PERSIST project is developing a multimodal sensor network for the remote monitoring of patients. The enumeration and classification of CTCs will be integrated in this platform by means of the novel microfluidic technology provided by RUBYnanomed.

Author: RUBYnanomed

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