Dr. Pashtoon Kasi on the impact of circulating tumor cells on clinical research
Why circulating tumor cells complement rather than replace ctDNA: access to cell-surface drug targets, faster turnaround, and multiple analytes from a single blood draw.
Recorded at the RareCyte booth at AACR, Dr. Pashtoon Kasi of City of Hope makes the case that circulating tumor cells (CTCs) are not a replacement for circulating tumor DNA (ctDNA) or tissue testing but a complement that reaches what ctDNA can miss. His argument turns on cell-surface protein targets: where ctDNA reports mutations and amplifications, isolating the intact cancer cell lets a lab measure the surface proteins that antibody-drug conjugates and newer theranostics are built to hit. Kasi also points to speed and sample economy, describing a CTC readout within a day or two of collection and a single blood draw that still leaves plasma for ctDNA and captured cells for downstream sequencing.
In this video:
- Kasi frames CTCs as one of the earliest forms of liquid biopsy, set aside for years because isolating the cells for analysis was not yet practical.
- Where ctDNA reports mutations and amplifications, CTCs expose the cell-surface proteins that antibody-drug conjugates and theranostics are designed to target.
- Beyond counting cells, he describes CTCs as an integral biomarker: enumeration and kinetics can track and help predict response to therapy.
- His rule of thumb for peers: almost any marker a lab can read by immunohistochemistry under the microscope can be adapted to a CTC-based analysis.
- On turnaround, Kasi reports a CTC enumeration-plus-expression readout within a day or two of collection, against the 7-to-10 days he cites for the best ctDNA and NGS assays.
- Because CTCs sit in the buffy coat, one lower-volume draw still leaves plasma for ctDNA and captured cells for single-cell sequencing, supporting multi-analyte liquid biopsy.
Full transcript
Interviewer: We’re here at AACR at the RareCyte booth. I’m here with Dr. Pashtoon Kasi from City of Hope. If you could just tell me a little bit about what you’ve been researching lately.
Dr. Pashtoon Kasi (City of Hope): I think the key thing that people often think about when they talk about liquid biopsies is circulating tumor DNA. I think it’s intriguing that some of the first liquid biopsies were actually circulating tumor cells. It’s just the fact that it wasn’t initially practical or feasible to isolate these cells to do analysis. Just like liquid biopsies, ctDNA is not meant to replace tissue testing. CTCs, the circulating tumor cells, are not necessarily meant to replace ctDNA, but they can help complement and provide insights that ctDNA can miss.
The biggest example, which is even more relevant at a conference like AACR as we talk about novel therapeutics and options, is markers that are cell-surface markers. Circulating tumor DNA can tell you about the mutations or amplifications. But cell-surface markers, proteomic markers for which there are antibody-drug conjugates and all these new theranostics — the target has to be present on the surface of the cancer cell. And if there was a way to isolate the actual cell and do the expression, that’s what CTCs can provide: not just as a prognostic marker, but also as an integral marker, as opposed to just quantifying, which you can still do. You can enumerate the CTCs, so the kinetics predict the response to therapy.
But in terms of being nimble enough to make a new marker as you get more drugs and targets: anything and everything you can do by immunohistochemistry under the microscope, I tell my colleagues and peers, you could probably do on a CTC liquid-biopsy-based analysis as well. It’s just like the work we’re presenting at AACR now.
Interviewer: And what do you see as the impact of CTCs in clinical research?
Dr. Pashtoon Kasi (City of Hope): Again, going back to what the impact of liquid biopsy as a whole is, it’s not going to replace tissue testing, but it makes it a safe, non-invasive, feasible, real-time option. With CTCs, you’d be surprised to know that you can get CTC analysis within a couple of days, whereas even for the best of assays, ctDNA, it’s 7 to 10 days. So as we think about integrating this into clinical trials or thinking about translational studies, using them in real time, often the bigger question is how quickly can you get these results back?
The enumeration followed by biomarker expression on any kind of CTC platform — we were pleasantly surprised to note, and it’s been an ongoing thing, that it’s within a couple of days. Pretty much as soon as you can get the specimen, you can get the result read out within the next day or two. That’s not always feasible with NGS-based MRD or ctDNA assays. So, again, this is not going to replace ctDNA testing, but for the question where you need the cell-surface membrane, that’s where it can complement.
Not to forget, with the CTCs on the slides you can also still do single-cell sequencing. You can still do downstream mutation analysis. As we think about one-, two-, four-analyte biopsies, the CTCs are often in the buffy coat, and from a technical standpoint you still have your plasma that you can use for whatever other analysis. So as we think about less volume and more multi-analyte analysis, a platform like this that offers CTCs paired with other analyses gives you what other assays will miss.
Transcript prepared from the recorded interview’s automatic captions and lightly edited for speaker labels, obvious caption artifacts, and the spelling of proper names (the interviewee’s name and institution were corrected against the video title); the speakers’ words are otherwise reproduced as spoken. Turnaround times and other specifics are the speaker’s own and may differ from formally published values.
