ctDNA, Liquid Biopsies, Methylation, NGS: What Does It All Mean?

Firstly, thank you, Corrine, and thank you, Sam.

Actually, it really is a pleasure to be here and speak with you all and to share my experiences actually with liquid biopsy over time.

So a liquid biopsy, most conventionally, it is a blood-based test where there may be fragments of DNA from a cancer that is circulating.

And what a liquid biopsy has done is been able to really characterize those fragments to give us insight into the tumor that can help understand the right treatment approach for a patient.

What's interesting is most of what is now regarded as liquid biopsy refers to circulating tumor DNA.

But as a broader term, liquid biopsy couldn't include circulating tumor cells or circulating tumor DNA.

Circulating tumor DNA refers to the shedding specific DNA fragments from a tumor into the blood, and that is then characterized.

What's interesting is that we all have DNA that is circulating through our blood.

And if we're running a marathon, if we are exercising, if we're sick with an infection or sepsis, we may have higher amounts of DNA that's being shed from our normal cells.

In a patient who has cancer, the cancer itself may be shedding DNA.

And that is referred to as circulating tumor DNA, which is distinct from CF DNA or cell-free DNA, which may be the wild type or normal DNA that we

all have in our bloodstream.

And so it may be characterized now where from a traditional blood tube, the samples are spun down plasma is filtered.

And then from that plasma, genomics can be done on the small fragments of DNA that exist in that plasma.

So that's kind of some of the nuts and bolts in logistics.

There are some technical points regarding the actual fragments and how those fragments can then be further characterized.

Some of that has to do with the size of the fragments and where the specific kind of intentions are around detecting fusions or amplifications or specific mutations that can then guide treatment.

Thank you so much for that initial overview.

I know a lot of our listeners probably have wondered, like, what is the difference between ctDNA, you know, CF or cell-free DNA? And are there any other analyzer components that can be measured?

Yeah, so historically, actually, there were a few others.

So extracellular vesicles were evaluated at one point.

And basically what that may refer to is there may be small liposomes and such that can carry some DNA fragments, may actually even carry some RNA fragments.

And that was when particular... interest is, could there be a better use of some of these materials to kind of better characterize the right genomic signatures? But historically, I think the big two types were ctDNA and circulating tumor cells.

And the circulating tumor cells referred more to actual cancer cells that could be filtered and then studied and then quantitative for further evaluation.

and even molecularly characterized with certain fusion partners of the androgen receptor and prostate cancer, where that was kind of a big undertaking with circulating tumor cells specifically.