Metastasis, the leading driver of cancer-related mortality, is thought to originate from the dissemination of rare cancer cells from the primary tumor into the blood stream. These precursors of metastasis are referred to as circulating tumor cells (CTCs) and offer a unique opportunity to gain molecular insight into the primary tumor from a simple blood draw. Additionally, individual tumor cells release tiny particles, or extracellular vesicles (EVs) at a release rate upwards of 10,000 EVs per day. As a result, interest in CTCs and EVs is rapidly growing due to their high potential to deliver an easily accessible set of cancer biomarkers. However, the low-frequency number of CTCs in the peripheral blood of cancer patients (1 CTC per 109 blood cells), and the small size of EVs (50 – 200 nm) has limited their potential for clinical translation. A common characteristic of CTCs and EVs is the expression of surface markers or antigens from their “parent” tumor. Exploiting their biological resemblance, I developed unique immunoaffinity-based microtechnology platforms that enabled the efficient capture and characterization of CTCs or EVs. The platforms facilitated off-chip genotyping analysis of CTCs and EVs, demonstrating their potential to deliver an accurate snapshot of the primary tumor. Next generation RNA-sequencing analysis of a cohort of breast and glioblastoma (GBM) cancer patients processed with these devices revealed thousands of variant genes related to disease progression, development of chemoresistance, and the epithelial to mesenchymal transition of cancer cells. Furthermore, the remarkable specificity of the platform allows identifying hallmark transcripts that define cancer subtypes (e.g., classical, mesenchymal, neural, and pro-neural) suggesting that the degree of heterogeneity within the tumors can also be recapitulated through CTCs or EVs. Overall through microfluidic isolation of blood-based biomarkers, my long-term goal is to develop clinically relevant devices that provide complementary data to help better guide patient diagnosis and treatment.
Dr. Reátegui is a postdoctoral research fellow at Harvard Medical School and the Massachusetts General Hospital Cancer Center in Boston. He earned his B.S. at the Universidad Nacional de Ingeniería in Mechanical Engineering (Lima, Perú), and his Ph.D. at the University of Minnesota in Mechanical Engineering, where his research focused on the development of inorganic biomaterials and polymeric nanointerfaces with tunable properties for reversible encapsulation of proteins and cells. His current research focuses on the development of microtechnologies, biomaterials, and biopreservation strategies for high-throughput sorting and molecular profiling of circulating cancer biomarkers; as well as the development of infection/inflammation on-a-chip devices for the biophysical and molecular characterization of immune cell interactions with pathogens.