Examining the Role of ctDNA

EP: 1.ASCO GI 2023: SUNLIGHT Study

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EP: 2.Examining the Role of ctDNA

EP: 3.Real-World Evidence (RWE) Supporting Use of ctDNA

EP: 4.Utilizing RWE to Address Unmet Needs for CRC

EP: 5.ASCO GI 2023: SPOTLIGHT Study

EP: 6.Opportunities for Innovation in GI Cancer Treatment Landscape

John L. Marshall, MD: We use the term ct [circulating tumor] DNA, or cell-free DNA, a lot nowadays in our oncology clinics. I think we need to be very clear about what exactly we’re talking about. On the one hand, we need to know the molecular makeup of a particular cancer, we need to know it in lung cancer, breast cancer, colon cancer, you name it. There has been new technologies developed to try and identify the molecular abnormalities in the patient’s tumor from the blood. And if you think about what this means, it means that cells have to have died. And those cells are like trash that is floating in the blood when a needle happens to be in there. And then the technology is just amazing to be able to look in this big haystack of molecular stuff, a lot of which is in fact DNA. Some of it is the person’s DNA, some of it is the tumor DNA, if you will, the trash and being able to pick out which molecular abnormalities are there. A RAS mutation, an EGFR mutation, etc. The technologies are evolving to allow us to find these abnormalities, which will then guide our therapies. Now, as a cautionary note, yes, the technology is getting better, but it has not yet improved itself over the standard, which is accessing the tumor by a biopsy and doing genetic testing on the actual tumor itself. That remains the gold standard. But you could see how doing a blood test and being able to do one serially would be very useful. So that’s when I think of doing liquid biopsies. That’s the language I use for that. I’m looking for specific genetic abnormalities from a patient’s known tumor.

Now, the other technology is for minimal residual disease [MRD]. It’s a different question. This is, is there still cancer there or not? And different kinds of technologies are being developed that are trying to find the presence or absence, not so much worried about which mutations, [but] are there cancer mutations in the blood at this moment. And [MRD] means there’s still cancer around somewhere. This was first championed in hematologic malignancies, newer technologies using tissue-informed testing. What this means is you actually take the tissue and figure out what mutations you’re going to look for [in] that individual patient. And then when your needle goes in and you take the blood, you can actually be much more specific, much deeper in your analysis, so that you can find fewer needles in the haystack. And this [has] really been some transformative technology on MRD. This can also evolve to this world of using this test as a very expensive, say, tumor marker, CEA [carcinoembryonic antigen], for example, is there more or less tumor alive, slash dying, with a treatment. So not only MRD but also tracking the progress of the benefit of treatment.

Transcript edited for clarity.