Circulating tumor cell counts are powerful prognostic factors for cancer patients. Recent research has found that they can be quite heterogeneous – similar to the cells of the tumor they shed from. Novel tools that analyze the different phenotypes can reveal their full potential as biomarkers in oncology clinical trials.
Circulating tumor cells are shed from solid tumors and released into the bloodstream. Traveling through the body, they can develop into metastases. Their presence in the blood may, therefore, provide an essential prognostic indicator in cancer diagnostics.
Current diagnostic methods determine tumor cell counts per unit of volume. Below a specific threshold value, the patient is considered to have a good prognosis.
Along the same line, these tumor cells are used as biomarkers in oncology clinical studies: If the new treatment is effective, circulating tumor cell counts are expected to decrease.
Tissue or liquid biopsy?
Circulating tumor cells are isolated from liquid biopsy samples – typically blood samples. Because blood draws are less invasive than tumor biopsies, the burden on the patient is significantly lower. Therefore, more samples can be obtained, providing a more comprehensive understanding of biological effects in oncology clinical trials.
Liquid and tumor biopsies do not always contain comparable cell types, but both sample types provide important and complementary information.
“Liquid biopsy samples are biased towards those cells that are more easily released into the bloodstream and therefore represent the most invasive subpopulations of the tumor,” said Jesus Garcia, Scientific Liaison at Precision for Medicine, a global precision medicine clinical research organization.
Not all circulating tumor cells are the same
Current methods separate circulating tumor cells from healthy cells based on the interaction of antibodies with cell surface antigens. However, heterogeneous subpopulations of these tumor cells have been identified that show a variance in surface antigens and even a loss of those markers needed for separation.
The role of these subpopulations and their impact on cancer development is still largely unclear and requires intensified research activities.
“We believe that antibody-based methods carry a risk of missing those circulating tumor cells that have evolved away from the classical subtypes and of losing the information we could gain from them,” Garcia stated.
Isolating the complete set
To obtain the full spectrum of circulating tumor cell types, Precision for Medicine offers a novel microfluidics-based separation method called ApoStream. It was co-developed and co-funded by ApoCell, Inc. (acquired by Precision Medicine Group) and the U.S. National Cancer Institute for the enrichment of rare cell types.
Instead of antibody-antigen interactions, ApoStream separates cells based on physical differences between tumor and healthy cells, including cell wall rigidity, conductivity, and diameter.
“As a result of these variations, the cells have different dielectric properties. By applying a suitable electric frequency, we can separate circulating tumor cells on a microfluidic channel surface whereas healthy cells stay in the flow-through,” Garcia explained.
Revealing the full potential of circulating tumor cells
Once the tumor cells have been separated, they can be immobilized, stained, imaged, and counted, followed by a thorough biochemical characterization.
“Based on the requirements of our clients, we apply a set of established circulating tumor cell surface antigens, complemented with customized biomarkers relevant for the individual oncology clinical trial,” Garcia said.
In addition, circulating tumor cells can be analyzed at the DNA and RNA level or cultivated for functional assays. Ongoing experiments at Precision for Medicine study the differences between the tumor cells of tissue and liquid biopsies from all possible perspectives for more insight into tumor heterogeneity and cancer development.
Dedicated sample management for pharmacodynamic studies
The use of low-invasive samples for oncology clinical trials permits conducting pharmacodynamic biomarker studies to analyze disease progression and biological effects.
With study sites often spread across the world, proper sample management is mandatory to ensure the rare cell types stay alive for separation and characterization.
As part of their integrated Tissue & Liquid Biopsy Profiling workflow, Precision for Medicine has established a dedicated sample management system. It includes validated temperature-controlled blood draw kits that maintain room temperature and are fully compatible with the ApoStream platform.
Together, these methods offer new possibilities to obtain information from circulating tumor cells in diagnostics and clinical trials.
Interested in learning more about how Precision for Medicine helps using the full potential of circulating tumor cells for oncology clinical trials? Visit the company’s website here!
Header image via Shutterstock.com, all other images courtesy of Precision for Medicine.
This article was originally published in July 2021.