Liquid Biopsy Approach Enhances Detection of Aggressive Breast Cancer Cells

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer and lacks targeted therapies. It spreads more readily through the bloodstream, and metastasis is responsible for most breast cancer-related deaths. Monitoring circulating tumor cells (CTCs), a key indicator of metastatic spread, has been difficult because these cells are extremely rare and poorly identified by existing markers. Researchers have now developed a blood-based approach that improves the detection of TNBC CTCs and enables real-time monitoring of metastasis using newly identified cell-surface proteins.

In research led by Baylor College of Medicine (Houston, TX, USA; www.bcm.edu), investigators focused on improving liquid biopsy techniques to reliably capture live circulating tumor cells from simple blood samples. Their approach involved developing a workflow to isolate live CTCs, first in mouse models of metastatic TNBC and then in blood samples from patients. Capturing live cells was essential because it enables detailed genetic and molecular analysis at the single-cell level.

After isolating individual tumor cells from blood, the team applied single-cell RNA sequencing to analyze gene activity within each cell. This allowed them to identify which genes were active and which proteins were present on the surface of TNBC CTCs. Through this analysis, the researchers identified four previously unrecognized surface proteins that distinguish TNBC CTCs from normal blood cells, providing new molecular “handles” for detection.

The study demonstrated that the proteins AHNAK2, CAVIN1, ODR4, and TRIML2 were present on live TNBC circulating tumor cells but absent from normal blood cells. When used together, these markers substantially improved detection sensitivity compared with standard CTC markers. The findings, published in Cancer Research Communications, showed that TNBC CTCs that were often missed by conventional methods became clearly detectable using the new marker combination, both in animal models and in patient samples.

Reliable detection of TNBC CTCs could allow clinicians to more accurately track disease progression, evaluate treatment response, and identify metastatic spread earlier. Because the method captures live tumor cells, it also enables deeper investigation into how metastasis occurs and why some cancers resist therapy. The researchers also found that these markers appear in other cancer types, suggesting the strategy could be adapted to improve CTC detection across multiple aggressive cancers in future studies.

“We are very pleased with our approach to identify CTCs in blood,” said corresponding author Dr. Chonghui Cheng. “We were excited with the results with blood from patients with metastatic TNBC.”

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