Liquid Logic: Circulating Tumor Cells Provide Valuable Insights

November 1, 2018
Liquid Logic: Circulating Tumor Cells Provide Valuable Insights
[Source: Olga Efimova / EyeEm / Getty Images]

Camille Mojica Rey, Ph.D., Contributing Editor

Widespread study of circulating tumor cells (CTCs) began in the early 2000s. Since then, the goal has been to replace expensive and invasive surgical biopsies with relatively simple and inexpensive CTC-based liquid biopsies. However, the translation of CTC-based liquid biopsy technology from research labs to the clinic has been moving forward slowly. A review published this year in Current Oncology Reports on the use of liquid biopsies in metastatic prostate cancer listed 15 platforms as examples of those used in research for CTC enrichment and detection. Yet, CellSearch, cleared by the FDA in 2008 for CTC enumeration, has been the only platform approved for clinical use in the past decade. And it is only approved for use in breast, prostate, and colorectal cancer patients.

Currently, physicians use CellSearch to count the number of CTCs in a 7.5-mL sample of blood. These counts have proven useful in prognosis and monitoring in the three types of cancer for which the technology is approved. In advanced prostate cancer, for example, 5 or more cells in a 7.5-mL sample has been shown to be associated with a worse prognosis. Physicians also use continuous counts of CTCs in monitoring the efficacy of a treatment. Though useful, this is far from fulfilling the promise of CTCs.

Researchers are hoping recent clinical findings will help move CTC-based liquid biopsies into the clinic more quickly. In addition to counting CTCs, they are now characterizing them and using that information to successfully make treatment decisions. Physician researchers are investigating the use of multi-parametric tests that will utilize both CTCs along with another blood-borne analyte—circulating tumor DNA (ctDNA). In addition, biotech companies, in collaboration with academic researchers, are working to introduce new, more sensitive CTC retrieval platforms—and get them FDA approved.

Characterizing CTCs

In a study published in July in JAMA Oncology, researchers from Memorial Sloan Kettering Cancer Center, the Royal Marsden Hospital in the U.K., and Lawson Health Research Institute in Canada showed that they could use a characteristic of CTCs to predict the optimal treatment for patients with advanced prostate cancer. The blinded, four-year study utilized the Oncotype DX AR-V7 Nucleus Detect test to determine if the nuclei from CTCs taken from 142 castration-resistant prostate cancer patients contained a protein called AR-V7. It is one of the first tests to validate the predictive value of a liquid biopsy for therapeutic response and demonstrated survival benefit. The researchers found that patients who had this variant present in the nucleus lived longer when treated with taxane-based chemotherapy, while those who tested negative for nucleic AR-V7 lived longer when treated with hormone-targeting therapy using androgen-receptor signaling (ARS) inhibitors.