Research in the field of liquid biopsies has taken off at an exponential pace in the past few years. Several research studies have demonstrated the promise of peripheral monitoring as a tool for better managing the metastatic disease state and predicting tumor-free progression and survival in the future1.
Whether your clinical research lab is interested in studying multiple templates such as Circulating Tumor Cells (CTCs) and cell-free DNA (cfDNA) for biomarker discovery or focusing on a single template type, the LiquidBiopsy™ instrument combined with the Ion Chef™ system and the Ion S5™ sequencers offer your lab a seamless, end-to-end workflow for liquid biopsy cancer research.
PAUL Y. SONG: “As somebody who’s been an oncologist for 20 years and somebody who’s lost his own father to cancer, this has been an area where I believe we need to improve on…”
Trends in cancer research and testing
“When we look at how patients are treated and where patients in my own practice were treated, we relied so much on the primary tumor specimen as a guide, in terms of what might be a therapeutic option for this patient, but what we soon realized is that the metastatic setting is vastly different, that the cells that are in the circulation are genetically and phenotypically quite different from the primary tumor in terms of what they can respond to. In some respects the reason they’re still in circulation is they’ve been able to escape and sort of mutate in a way that has allowed them to survive. So one of the things that was so exciting about what we’re working on is we have the ability to isolate these cells, to find them in circulation as well as the cell-free DNA, to not only do genomic analysis but look at proteins, look at RNA, eventually look for PD-L1 expression.”
Trends in liquid biopsy research
PAUL W. DEMPSEY: “I think there are CTCs and cell-free DNA and exosomes are all rare events, and they also reflect different aspects of the biology in research samples. So being able to evaluate them in their plurality from a single sample gives us access to whatever the biological biomarker is going to be able to tell us, without us having to guess before we run a sample, what is the right answer. And really that’s, from a discovery perspective and a research perspective, the most important aspect. I think what’s happened with the advent really of desktop sequencer platforms is that the quality and the spectrum of molecular information we can garner now from a tumor sample has exploded. So what we found asking ourselves here in developing the liquid biopsy is: what is it that we can provide to the community that would best serve the development of tools that will help patients in the long-term?”
Thoughts on the Ion S5 systems
“Our approach in evaluating the S5 was to take the same sample with the same panel and run it in parallel on the PGM and the S5. For a start, that’s capable and that’s possible because the workflows and the chemistry are shared so we can build the library and run exactly the same library on the two platforms and that makes cross-validation a very straightforward affair. When we did that, we did that with a number of different panels, we saw that for the same library run in parallel, the performance was exactly the same, by any measure we could use to determine. The most important ones are: the uniformity of reads; the noise variables – how much background noise we get on a known negative sample; and our ability to call non-positives. All of those metrics, which is the most important for us, perform equally well on the two platforms. These are complex tests and so having a platform that is reliable and gives high quality data and has a large – being paired with a Chef has a large automated step so that failures – means that a relatively complex test can be ported into a new environment quickly. It can be up and running with relatively unsophisticated labs very quickly. The most important thing for us getting the S5 in was the bandwidth it allowed us. So because of the three different chip sizes, we have the capacity to go from what we used to be able to do on the PGM, which was one sample per run, up to as many as 20 samples per run on the S5. So we have the spectrum now to accommodate a much larger sample load and accommodate the samples we’re running through the lab. As we move forward I would like to see all these technologies, through the decrease in price of the technology and the testing, and the increased sensitivity of the platforms as we move forward, to become more useful detecting disease at points where right now we don’t have good tools. And that is the only thing really that’s going to change – move the needle in terms of the number of people who suffer from cancer.”
For Research Use Only. Not for use in diagnostic procedures.
1.] Bardia A, Haber, DA. Solidifying Liquid Biopsies: Can Circulating Tumor Cell Monitoring Guide Treatment Selection in Breast Cancer? JCO Nov 1, 2014:3470-3471; published online on July 14, 2014;