ESMO 2014-LIQUID BIOPSIES

Liquid biopsies are non-invasive blood tests that detect circulating tumour cells (CTCs) and fragments of tumour DNA that are shed into the blood from the primary tumour and from metastatic sites

• Date: 29 Sep 2014
• Author: Giuseppe Curigliano
• Affiliation: European Institute of Oncology, Milan, Italy
• Topic: Translational research /  Basic science

Article extracted from the ESMO 2014 onsite newspaper.

This technology has enormous diagnostic and treatment implications for oncology and I believe it is poised to transform clinical practice. As an integral part of precision medicine, the importance of liquid biopsies was highlighted in a Special Session on Saturday, at which experts from around the world discussed its potential and limitations.

So, what’s all the fuss about? Tumour genome sequencing to inform treatment decisions is already central to the management of many patients with cancer and I have witnessed this change the hallmark of cancer care. Tailored therapy relies on the identification of the correct molecular tumour target. Currently, tumour biopsy tissue, generally from the primary tumour, is used to determine molecular targets at a single time point, before treatment commences. These biopsies carry some risks for patients, they are painful, they are costly and, importantly, the process takes time. Also, given the complexities of tumour heterogeneity, both within a tumour and between a primary tumour and metastases, a tissue sample may not be a true representation of the molecular profile. A liquid biopsy, on the other hand, may capture the entire heterogeneity of the disease. What is more, tumour genotypes are notoriously unstable and prone to changes under selection pressure. In this regard, liquid biopsies offer what tissue biopsies cannot, due to risks to the patients and cost; the opportunity to take serial samples in order to monitor tumour genomic changes in real time. This will allow clinicians to ensure that the therapy they have selected, based on a particular molecular target, remains relevant and observe the emergence of any resistance. Instead of waiting for information from scans, we may be able to identify at an earlier stage if a treatment is not working and to spare the patient the unnecessary toxicity of a drug that no longer provides any benefit. At the same time, we may be able to observe if any new molecular targets appear that could be suitable for treatment. All this could help to provide patients with the right treatment for the right target without delay.

Liquid biopsies also present us with a unique opportunity to move forward with our understanding of metastatic disease development and they may help to identify signalling pathways involved in cell invasiveness and metastatic competence. Ultimately, at some point in the not too distant future, these tests will be used in the diagnosis of cancer. This will revolutionise cancer care, providing clinicians with rapid access to information on a molecular level at diagnosis, thereby optimising treatment choices.

In terms of samples, CTCs have been the most studied. While these cells are relatively rare and require sensitive collection and enrichment technology, they provide information at both the genetic and cellular level. However, cell-free tumour DNA (cfDNA) is emerging as an effective alternative to CTCs, with the benefits of easier collection and analysis. Today, a Poster Discussion Session on Trials and Tribulations in Oncology: Future Approaches (13.00 – 14.00, Pamplona) will feature two abstracts on cfDNA liquid biopsies: one on the use of serial next generation sequencing of cfDNA to monitor response and progression during administration of drugs in the phase I setting (Abstract LBA6) and another on the de novo detection of cfDNA in patients with refractory cancer (Abstract 1571PD). These studies should help us to build on our understanding of the type of information cfDNA-based liquid biopsies can give us.

We do know that standardisation will be a key factor in ensuring consistency between centres and in determining its clinical success. It is crucial that we standardise the assays used to evaluate cfDNA and also define the optimum sampling specimen (i.e. serum or plasma). In fact standardisation across the board would be ideal: blood collection, processing, storage, and DNA extraction, quantification, analysis and reporting of data. Future development of liquid biopsies will need to provide a cost-effective analysis, mainly identifying the genes known to be recurrently mutated in each tumour. Therefore, developing standardised methodologies for cfDNA analysis and validation in large prospective clinical studies is mandatory for the implementation of the liquid biopsy approach in the clinical management of cancer patients.

In the field of oncology, we see so many innovations come and go, without lasting impact. Will the promise of liquid biopsies be a clinical reality? It is hard for me to not to be excited about the benefits they can offer to patients and I believe that they will be invaluable to cancer research and treatment.

I would like to thank the Congress Daily Editorial Team of Evandro de Azambuja (Editor-in-Chief), Markus Joerger and Floriana Morgillo (Associate Editors) for giving me the opportunity to write this editorial.