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The Liquid Biopsy Workflow

Anders Stahlberg works both in the academic setting as Associate Professor at the University of Gothenburg and in the clinical setting at Clinical Genetics & Genomics, Sahlgrenska University Hospital. Together with his colleagues, this means all aspects of circulating cell-free tumour DNA are covered; from basic science and development, understanding why and how liquid biopsies should be undertaken, to clinically focused questions that the patient will hopefully benefit from.

Ahead of the Liquid Biopsies Congress later this year, we spoke to him about his work.

You’re going to be presenting on analysing cell-free tumour DNA at the event. Can you tell us a bit more about that?  

We work with the entire process in the liquid biopsy workflow from sampling to data analysis. Our specialty is working with several ultrasensitive techniques to do these analyses with our expertise in single-cell/molecule analysis.

When it comes to the real applications, we work quite broadly. Our main interest is to monitor patients and see how they respond to treatment and to detect the potentially resistant mechanisms. ­­

One approach we have is to monitor each patient’s specific mutation over time to see if our technology developments are useful. For example, we work with childhood cancers with a lot of private mutations. Here, the common hot-spot panels are not very useful, so instead we personalize the analysis for each patient and monitor them over several years.

We try to cover the whole aspect of analysis with a focus on circulating tumour DNA, bringing into focus the pros and cons of the workflow and trying to integrate that into the other data that is generated in the clinic and evaluate the use of these new molecular analysis.

What’s the process of this type of liquid biopsy? How was it developed?

We wanted to apply commonly available techniques, but they weren’t sensitive enough to be able to use them on a very low amount of DNA and were flexible in changing what it would detect. Around five years ago, we decided to develop our own technology with Tony Godfrey at Boston University called SiMSen-Seq. We use a unique molecule identifier, so in that sense, is similar to many other approaches. The beauty with it is it’s very simple and user-friendly.

It’s easy to adapt for very different applications beyond tumour biology. It can be adjusted for small panels, large panels, high throughput sampling. In fact, we’re also working on SiMSen-Seq2, which is even simpler, faster and will enable an easy automation process.

How can this technique further develop? How can you integrate it further into clinical work? What are the developments that you’d like to see to make it more efficient?

One thing is to shorten the overall process – sometimes you need the data in hours, a day or two days. In principle, our approach takes just a few hours, but it’s the whole integration process that’s interesting, including sampling and sequencing. Can we extract DNA faster? How to provide data? Can the entire process be more integrated?

Also, can we be even faster when we need to generate personalized assays? How much validation do we need to do? How can we shorten the time lag between monitoring novel mutations to being able to monitor the patient?

There are a lot of proofs of concept studies with our and other techniques, they have proven that analysis of cell-free DNA are powerful and can be used in a wide range of applications. The question is – what does it take to implement and what are the applications and demand from the clinical side?

Are there any general developments that you’d be excited to see in the future?

It’s interesting to see when you have multi-analysis integration, when you can look at different analysis, when you start combining different types of data, integrating cell-free tumour DNA data with other types of data for example protein, metabolite, carbohydrate and RNA analysis as well as other approaches such as imaging.

To fully explore the potential of circulating tumour DNA it will be important with standardization, so common efforts to standardize and how to report data will be important in the future to utilize the full potential.

Anders Ståhlberg

Anders Stahlberg, Associate Professor, University of Gothenburg will be speaking on ‘Considerations when analyzing cell-free tumour DNA’ at the Liquid Biopsies Congress: Europe.

View the agenda to see what else will be covered at the Liquid Biopsies Congress: Europe. Don’t forget your ticket gives you access to all five meetings in the Research & Technology Series: Immuno-Oncology.

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