July 3, 2018 | Massimo Cristofanilli of Northwestern University is featured on this podcast from the Cambridge Healthtech Institute for the Next Generation Diagnostics Summit. Cristofanilli shares his perspective on the future of liquid biopsy, the complementary purposes of CTC and cfDNA technologies, and when one should expect clinical utility of liquid biopsies. Here is a sample of the discussion that takes place. Podcast
CHI: Now, in your opinion, are both CTCs and cfDNA important, or are they just redundant technologies?
Massimo Cristofanilli: I think this is a very important question because the field has been shifting from CTC to DNA without truly understanding what's the role of each modalities and technology. I think they are actually complementary in a way because the DNA of the naturally identifying mutations derives on the metastatic lesions can give us some information about the better therapy and the mechanism of resistance. So the CTC might only be informative of the metastatic process, but that's why it's more difficult to detect in all patients but in a faction of them. There are different phenotypes of CTC so technology have been tried to capture as much as possible. We went from immune magnetic to microfluidic systems that allow us to perform some basic morphology assessment and immune histochemistry analysis the cells will recover beside mutation and single cell analysis. Both of them allow us to study tumor heterogeneity. It appears to be clearly a problem when you're trying to define treatments and treatment resistance.
CHI: What do you want to see more in the liquid biopsy field?
Cristofanilli: I think it's time for the industry to incorporate liquid biopsy in patients' stratification and patients directed therapies. We have seen a number of retrospective analysis presented for metastatic breast cancer showing that patients with specific somatic mutations, such as ESR-1 mutations are resistant to aromatase inhibitors indicating the impact of this information. We have seen that, for example for the studies using tissue analysis for selection, this can be difficult to collect in metastatic studies and without ctDNA testing; the study will not allow to get this information in real time. We have seen that evaluating CTCs can help stratifying patients with aggressive vs. indolent disease, and this information still has to be integrated in the design of prospective clinical trials to show how our new treatments may have an impact on overall survival. So I think the incorporation (of liquid biopsy) into trial design is almost a necessary step and, what I would like to see for the field (therapeutics and diagnostics) and all the technologies to work together.