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.
Guiseppe Curigliano, Congress Daily, Guest Associate Editor, European Institute of Oncology, Milan, Italy
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.
http://www.esmo.org/Conferences/Past-Conferences/ESMO-2014-Congress/News-Articles/Liquid-biopsies-Tumour-diagnosis-and-treatment-monitoring-in-a-blood-testThis post is on Healthwise
Company Bets on Catching Cancer With 'Liquid Biopsy'
JAN 10 2016,
by
Gene sequencing company Illumina is betting it can diagnose cancer in people long before they have any symptoms at all with a blood test called a liquid biopsy.
The San Diego-based firm launched a spinoff company Sunday named Grail, with obvious references to the "Holy Grail."
"The holy grail in oncology has been the search for biomarkers that could reliably signal the presence of cancer at an early stage," said Dr. Richard Klausner, a former director of the National Cancer Institute who's a member of the new company's board of directors.
The plan is to use Illumina's super-fast genetic sequencing technology to look for genetic material from tumor cells in peoples' blood long before they have any evidence of cancer. The test would check for genetic mutations known to be found in tumors.
Something similar is already done sometimes in people who already have cancer. The liquid biopsies are used to see how well cancer treatment is working.
Blood Test May Detect Pancreatic Cancer in Early Stages 1:34
Some big names in investing and cancer researcher are signing on for the enterprise.
Some big names in investing and cancer researcher are signing on for the enterprise.
They include Amazon founder Jeff Bezo's Bezos Expeditions, Microsoft co-founder Bill Gates and Sutter Hill Ventures. Klausner; Dr. Jose Baselga, physician in chief at Memorial Sloan Kettering Cancer Center and president of the American Association for Cancer Research; and Dr. Brian Druker, director of the Oregon Health & Science University, have signed on to the advisory board.
"We hope today is a turning point in the war on cancer," said Jay Flatley, Illumina's chief executive and chairman of Grail.
"By enabling the early detection of cancer in asymptomatic individuals through a simple blood screen, we aim to massively decrease cancer mortality by detecting the disease at a curable stage."
It will be years before any such test could be designed, and it would have to be tested in thousands of people before regulators could consider approving it. Right now one of Illumina's whole-genome tests costs about $1,000, so it would be a pricey cancer screening test unless that cost can be brought down.
And while tumors are known to drop bits of genetic material into the blood, cancer experts caution that some early cancers may not secrete DNA fragments and require other types of detection.
Cancer is the No. 2 killer overall in the United States, but it's neck and neck with heart diseases.
Last week, the American Cancer Society projected that cancer would be diagnosed in close to 1.7 million Americans this year and that it would kill nearly 600,000. Most deaths are of people whose cancer had already spread before it was treated.
The U.S. Food and Drug Administration has been very skeptical of blood tests that claim to diagnose disease before people have symptoms.
In September, the FDA slapped Pathway Genomics over its "liquid biopsy" testthat claims to do what Grail proposes.
The FDA said the company had not shown the $699 test worked, warned that it "may harm the public health" and said the company hadn't applied for proper regulatory approval.
