Emerging Strategies in Multi-Cancer Early Detection - Episode 8

Advancements in Multi-Biomarker Cancer Testing

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Key opinion leaders review the rationale behind multi-biomarker approaches and how they're shaping the future of cancer detection and research.

Transcript:

Jon O. Ebbert, MD: Let’s talk with Dr Beer a little bit about evolving approaches to multibiomarker class and test design. Maybe you could walk us through, Dr Beer, a little bit about the rationale surrounding a multibiomarker approach to testing, including methylation, mutations, proteins, and aneuploidy.

Tom Beer, MD, FACP: Sure. That approach reflects a number of years of work at several academic laboratories and within Thrive and Exact Sciences. Thrive is now a part of Exact Sciences. A lot of [experts] have contributed to this approach. The approach is really rooted first in a deep understanding of cancer biology. Credit there, I think, goes to a team at Johns Hopkins Medicine led by Bert Vogelstein, [MD,] who really got this started with a 2 biomarker class approach, looking at the analysis of cancer-causing mutations and protein biomarkers that are known to be associated with cancer.

That was the basis for the initial iteration of what is now known as the Exact Sciences tests, which yielded encouraging results. Since then, collaborators at Mayo Clinic and scientists at Thrive and Exact have examined additional biomarker classes. And the idea really is to develop a test that is robust and reproducible by looking at complementary signals from a range of understood cancer biomarkers. So that we do the very best job possible of detecting cancers early and hopefully also learn something about the biology of those underlying cancers as we go.

Jon O. Ebbert, MD: What insights have the prior studies that we talked about here today revealed? And how has this influenced current and future design?

Tom Beer, MD, FACP: So the PATHFINDER study that I discussed earlier certainly provided proof of concept about the value of DNA methylation as a biomarker to be used in the development of outside tests. That DETECT-A study, which Adam discussed earlier, examined an early version of what is now the Exact Science subtest that involved mutational analysis, as well as protein biomarker analysis. And those 2 were combined into a single blood test. There, too, we saw the proof of concept that those 2 biomarker classes enable the early detection of cancer. And interestingly, the signals were largely complementary.

So when one takes a more detailed look at the 26 cancers diagnosed with DETECT-A, the large majority of them were detected through the detection of one or the other biomarker class, but not both. So that showed us that complementary biomarker classes can really reinforce each other. A number of small developmental studies reported by scientists at Johns Hopkins and Exact Sciences and at Mayo Clinic have looked at the addition of the additional biomarker classes incorporated into the current investigational version of the Exact Science [test]. And some suggest that includes a measure of aneuploidy, which is a DNA structural change that is common in cancer, as well as an assessment of DNA methylation. So the current version of that test that we’re evaluating includes up to 4 biomarker classes, [although] we’ve yet to put that to the test in prospective studies. So that’s a project that we’re looking forward to.

Transcript is AI generated and edited for readability.