Advances in Liquid Biopsy Methods: Circulating Tumour Cells (CTCs), Circulating Cell-Free Nucleic Acids and Exosomes

The last five years have seen substantial growth of interest in the development of liquid biopsies – non-invasive blood tests that allow the isolation of circulating tumour cells (CTCs) or circulating cell-free nucleic acids (cfDNA and cfRNA), originating in the primary tumour or multiple cancer sites.

These activities are driving changes in cancer research and drug discovery, as well as in diagnostics and clinical trials. In turn, these are increasing the demand for laboratory methods to isolate and characterise CTCs and circulating cell-free nucleic acids, as scientists and clinicians seek to better understand this growing field.

Techniques to isolate and characterise CTCs and circulating nucleic acids are developing rapidly, both of which potentially offer important diagnostics advantages over established biopsy approaches. Therefore, it seems likely that liquid biopsy approaches will be standard practice amongst the array of tests used in research, drug discovery, diagnostics and clinical trials. Developments are also been seen in the isolation and characterisation of exosomes and the characterisation of circulating nucleic acids in other biofluids, including urine.

Despite exciting developments in these fields, fundamental questions remain unanswered.

Nevertheless, despite the excitement these developments are creating, important and fundamental questions remain unanswered. In the case of CTCs for example, a number of cell types are now grouped under the ‘CTC umbrella’, raising questions of the importance of particular subtypes in cancer progression and how they are selectively detected, isolated, characterised and quantified, alongside whole CTC populations and other CTC subtypes.

There are also questions on how these techniques are validated and the accuracy and reproducibility of such tests established, allowing valid, consistent and dependable comparisons of CTC findings between different groups and studies. This is particularly the case in the CTC field, where many different platforms and mechanistic strategies have been developed to isolate or enrich CTCs, which may inherently favour certain CTC subtypes over others. While these diverse capabilities are enhancing scientists’ understanding of CTCs and CTC subtypes, questions remain when it comes to choosing particular techniques over others. This underlines the need for adequate and well-designed validation studies to enable the correct choices to be made for the benefit of patients.

There are also important unanswered questions relating to circulating cell-free nucleic acids (i.e. cfDNA and cfRNA). These include linking the genetic fragments with the tumour tissue of origin and identifying the markers indicative of the development, stage or progression of a particular cancer on the one hand and potential therapeutic interventions on the other. Work is also progressing in the area of exosomes and the characterisation of tumour cells and cell-free nucleic acids in other biological fluids, all of which have implications in generic and personalised diagnostic and therapeutic strategies in the cancer field.

Therefore while CTCs, circulating cell-free nucleic acids, exosomes and related activities are driving the development of new laboratory, diagnostic and therapeutic approaches, it is imperative that these and other important questions are answered, to maximise on new opportunities for better diagnostic methods and treatments for patients, while minimising the risk to innovators and developers in these fields.

As with all developing fields, uncertainties on the one hand and differences of opinion and strategy on the other, are reflected in the diversity of activities and practices seen in the laboratory. To give just a few examples, more than a dozen CTC subpopulations (e.g. circulating tumour stem cells, epithelial tumour cells, epithelial-to-mesenchymal transition cells, CTC Clusters, circulating endothelial cells, apoptotic CTCs etc) are now being researched and 60+ CTC markers are being investigated. Different approaches being taken to generic CTC measurements, such as differentiating CTC subtypes, CTC counts, time-dependent changes and CTC size or morphology.

More than 30 CTC enrichment or detection platforms have been developed, covering multiple mechanistic approaches.

More than 30 CTC isolation and enrichment platforms have also been developed, covering multiple isolation, enrichment and detection mechanisms. Equally, more than 15 non-molecular methods are used in the CTC arena and 20+ molecular techniques are used in the characterisation of CTCs and circulating nucleic acids. In all cases, these are now being used by scientists and clinicians to answer important questions in their own areas of research. These activities present considerable demands on laboratory suppliers supporting these diverse activities.

Laboratory Markets Ltd carries out end-user studies to assist suppliers and developers by profiling current and evolving laboratory market opportunities. With important advances being seen in the liquid biopsy field, Laboratory Markets Ltd has carried out two comprehensive studies of developments relating to CTCs, cell-free nucleic acids (cfDNA and cfRNA) and exosomes, to assist suppliers in supporting evolving laboratory needs in these growing fields. These studies analysed the activities and future plans of 482 experienced scientists and clinicians in the cancer field.

In the CTC field, these studies profiled growth, 3-year plans, costs, detection and enrichment platforms, CTC measurements, non-molecular techniques, molecular techniques, suppliers, enrichment markers, CTC subpopulations, molecular forms, clinical utilities, cancer types, limitations, drug R&D, companion diagnostics and other areas. In the circulating cell-free nucleic acids areas, these studies profiled growth, 3-year plans, costs, molecular techniques, suppliers, enrichment kits, molecular forms and biomarkers, clinical utilities cancer types, limitations, drug R&D and companion diagnostics.

Findings from these studies provide a wealth of market information to laboratory suppliers and developers in these fields. Full study details can be seen here…

 

For further information or to request sample data, please contact Claire Nicholson

Tel: +44(0)1904 848895 / +44(0)7550 079918

Claire@biopharma-research.com
Biopharma Research Ltd is the Exclusive Distributor of Laboratory Markets’ range of reports and research services.