For some time, researchers have known that circulating tumor cells exist in the blood of patients with both metastatic and localized solid organ malignancies. However, early technologies were not sensitive enough to pick up these rare tumor cells from blood. With rapid advances in technology, these “liquid biopsies” have become better characterized. There are three important components to liquid biopsies: CTCs, cell-free DNA, and exosomes. Each of these components provides a deep well of useful information, and Dr. Toner believes that every malignancy in the future will be characterized by analysis of the various components.
The team then developed chip technology borrowed from the advanced microprocessor production methods in the computing world. The first generation of CTC-chip utilized antibody-coated “nanoposts” etched on a chip. When blood passes through the chip, every cell interacts with the posts. For the first time, researchers were able to find enough viable tumor cells, in an efficient manner, to make a meaningful clinical impact. Over time, they found that tumor cells can evade detection even with if they interact with antibodies. These “stealth-CTCs” come in many forms and sizes, cover themselves with different molecules, are undergoing various stages of epithelial-to-mesenchymal transition, etc... In order to improve detection of more CTCs, the team developed the concept of “negative depletion”. Negative depletion is akin to finding a needle in a haystack by individually taking out all the hay until only the needle is left behind. In essence, the chip processes the blood to sift out known components of blood, such as RBCs and platelets, until all that is left are untagged CTCs. By doing this, researchers were able to overcome the obstacle posed by CTC heterogeneity.
The latest generation of CTC-chip utilizes microfluidics to perform size and epitope-independent capture of CTCs. These “labs on a chip” are small and portable – about the size of a CD. Using techniques adopted from the media industry, such as blueray technology, they can imprint the appropriate microscale structures on chips now with relative ease. Soon, researchers and diagnosticians will be able to quickly, and relatively cheaply, obtain untagged, viable CTCs from patient blood. The clinical uses for these kinds of cells will be the subject of an entire generation of research.
Dr. Toner concluded with several examples of the future of this technology, and what kinds of information can be gleaned from captured CTCs. This body of work constitutes one of the most monumental advances in medical technology of the century. As this paradigm-changing work continues to be developed, clinicians, patients, and researchers will be anxiously awaiting the day when cheap, portable, and powerful point-of-care medicine becomes a reality.
Presented By: Mehmet Toner, PhD; Massachusetts General Hospital
Written By: David B. Cahn, DO, MBS, Fox Chase Cancer Center
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA