Liquid biopsy is not a new concept; the blood has been interrogated for diagnostic markers for nearly a century. However, with the development of next generation sequencing and other tools in the last twenty or so years, the field has exploded in interest and advancement.
Although liquid biopsy is sometimes used synonymously with blood markers, the technology also encompasses the examination of other bodily fluids like urine, cerebrospinal fluid, saliva, pleural effusions, or ascites fluid. The right type liquid biopsy will depend on the molecular marker the clinician is looking for.
The probing of bodily fluids has its own advantages and disadvantages compared to tissue biopsies. The latter is often far more invasive and takes much longer than liquid biopsies. However, a lot more is known about the clinical validation of tissue biopsies. Perhaps the biggest advantage of their liquid counterparts is the ability to monitor drug response in real time, but more trials are necessary for their widespread clinical adoption.
Circulating tumour cells (CTCs) are a common object of focus for liquid biopsies. CTCs shed from primary tumours into the bloodstream and can provide insights into metastatic processes. Recent research indicates that CTC clusters may have greater metastatic potential than single cells. Various FDA-approved platforms exist for isolating CTCs, with ongoing research focusing on improving their clinical utility and understanding their role in tumor heterogeneity.
Another target is circulating tumour DNA (ctDNA). This marker is associated with tumour burden and can be analysed for mutations which can aid in monitoring and inform treatment. Many sequencing platforms are available which can analyse liquid biopsies, and for labs without a sequencer, qPCR can also be used to assess mutations, albeit in a more limited way.
Numerous clinical trials are underway to explore the efficacy of liquid biopsies, particularly in tracking treatment responses across different cancers. The potential of EVs as biomarkers and therapeutic tools is being investigated, although this area is still developing with fewer clinical trials compared to CTCs and ctDNA.
In conclusion, liquid biopsies present a promising avenue for cancer diagnosis and monitoring, with ongoing research needed to address technological and biological challenges for wider clinical adoption.
