Sample Preprocessing, Circulating Nucleic Acids, Cancer Biomarkers, and Clinical Data

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Ann Nguyen:

Hello. This is Ann Nguyen, Senior Associate Conference Producer with Cambridge Healthtech Institute. It's time for a podcast for the 2016 Leaders in Biobanking Congress, September 7-9 in Baltimore, Maryland. I'm pleased to have over the phone Dr. Anton Wellstein, Professor of Oncology, Pharmacology, and Medicine, and Associate Director of Basic Science at Lombardi Comprehensive Cancer Center with Georgetown University Medical School.

Anton, thanks so much for the chat today.

Anton Wellstein:

Thank you.

Ann Nguyen:

I understand your aim is to find targets amenable to therapy and to establish biomarkers to monitor treatment efficacy in cancer patients. You meanwhile have expertise in the collection, processing and storage of blood-derived biospecimens. How does your understanding of specimen storage inform your basic research, and what broader connections could we draw between those areas?

Anton Wellstein:

It's preprocessing, as they call it, of samples, which means collection and processing of those samples before we analyze them. It's a very important feature of quality control. To give you an example, it depends very much if you draw a blood sample how long you let that sit before you spin it down, how long it then takes to take that blood sample and freeze it for permanent storage, where if you isolate cells from a blood sample, obviously it's even more crucial.

I'm very much interested in the analyzed samples to see how that pre-analytical processing went. When I look at samples it's an important issue. Unfortunately very often we will not be able to get that information because it's not always recorded. I think it would be good practice to do that.

In a basic science lab we are very much used to that, but we have much more control over acquiring samples from animal studies, for instance, than we have in a … setting of a clinical trial. I think that pre-analytical processing should have a high priority in terms of collecting the specimen and recording that.

Ann Nguyen:

You'll discuss “Circulating Nucleic Acids in Cancer Treatment Monitoring” during your presentation on September 8. What's the main theme you'd like to convey to the audience of not only researchers but also biorepository managers?

Anton Wellstein:

There are two aspects of this. Number one, I think, is that the technology that has been developed over the last decade has become incredibly sensitive to detecting nucleic acids at very minuscule levels. We have been able to use different technologies, different properties … sequencing to really find very small amounts of non-abundant DNA or RNA in the circulation. Technology evolvement is really a key feature that the technology's available to analyze at low levels of nucleic acids and nucleic acid specimens that are of low abundance.

The biologic features, or the features that are relevant for the clinic or for treatment of patients or for monitoring of patients, is that we can, by going into the bloodstream – which means taking a blood sample or a liquid biopsy – repeatedly assess the status of a disease in response to treatment particularly in cancer where we have the option of looking for mutant DNA that is a signature of the cancer or cancer metastasis. The liquid biopsy in the bloodstream is a perfect representation of what's going on in that person's body. We have access to all compartments in the body at a given point in time because all compartments are connected to the bloodstream. That provides us with an opportunity to get a very holistic picture of the molecular status of a cancer in response to drugs.

I think that this will become routine to be able to monitor disease status by taking a blood sample at shorter intervals, say at a few days, weeks, or months. That's why I find this very exciting. It really dovetails well with the term that is used a lot, precision medicine, that we can really do longitudinal studies, not just a one, single-time biopsy from a tissue but we can follow it over time. If you think about cancer as a disease we are focused on, cancer is a systemic disease. It's not just a local disease. If it's a local disease you can deal with it with surgery or radiation.

Once the disease starts to spread in the body it becomes systemic. It also makes our diagnostics much more difficult because we cannot biopsy all the sites where the cancer has spread to. …if you take a liquid biopsy, you will get the information from all of those sites compiled in your sample. That's why I think a nucleic acid … technology developed to detect them and analyze them will really make a big difference in the way we go forward.

Ann Nguyen:

Finally, what challenges persist when it comes to linking cancer molecular markers with clinical information? And what needs to be done to overcome them?

Anton Wellstein:

The major challenge we face in the analysis of biomarkers from a circulation are the same challenges we face when we do any molecular analysis of human tissues. The tools that are developed for genomic analyses, for mutation analyses, that are in place and are being developed further will be the very same tools we use. In my opinion, these challenges that we face are the same in terms of analysis of complex datasets, be that for liquid biopsies or be that for tissue analysis. We are definitely still in the early phases of being able to connect clinical data on the one hand, with molecular data on the other hand, and to make sense of how these data predict sensitivity to treatment or resists the treatment.

I don't think that what we do is different from what people do in their analyses with tissues. I don't think that we will need to develop specific tools. We use the same tools that are there and that are applied. That is challenging because we're still in the early days of developing these tools.

Ann Nguyen:

Thank you for the insights, Anton. You'll be contributing even more during the conference as a speaker, chairperson, and discussion group moderator so we'll be eager to reconnect with you then.

That was Dr. Anton Wellstein of Georgetown University Medical School. He'll be speaking during the session, Biospecimens Link Cancer Molecular Markers to Clinical Information, at the Leaders in Biobanking Congress, happening in Baltimore this September 7-9.

To learn more from him, visit for registration details and enter the keycode “Podcast”.

This is Ann Nguyen. Thank you for listening.