Researchers at Baylor College of Medicine have developed a new method to improve the detection of aggressive breast cancer cells circulating in the blood, specifically for triple negative breast cancer (TNBC). TNBC is known to be one of the most aggressive forms of breast cancer and is more likely to spread to other organs through the bloodstream. Tracking these circulating tumor cells (CTCs) has been difficult due to a lack of specific markers.
The research team created a process that enhances the identification of TNBC cells from a simple blood draw, also known as a liquid biopsy. This approach allows for minimally invasive monitoring of cancer progression. The procedure led to the discovery of four new proteins on the surface of live CTCs, which are unique to these cells and not found in normal blood cells. Identifying live CTCs enables scientists to analyze genetic material from individual tumor cells and gain insights into how cancer spreads.
The findings were published in Cancer Research Communications, a journal from the American Association for Cancer Research.
"We developed a new workflow to isolate and analyze live CTCs, focusing first on mouse models of metastatic TNBC and then testing our findings in patient samples," said Dr. Bree M. Lege, former graduate student in Dr. Chonghui Cheng's laboratory at Baylor College of Medicine.
The researchers began by capturing rare live CTCs from mice with tumors by separating them from normal blood cells. They then used single-cell RNA sequencing to measure gene activity and identify cell-surface proteins present in TNBC CTCs.
Through this analysis, they identified four new markers: AHNAK2, CAVIN1, ODR4, and TRIML2.
"We were excited with the results with blood from patients with metastatic TNBC," said Dr. Chonghui Cheng, professor at Baylor College of Medicine. "In these patients, tumor cells were frequently undetectable using standard markers but became clearly visible when we applied the new marker combination."
This development could help doctors monitor disease progression and treatment response more accurately for aggressive breast cancers like TNBC. The ability to capture live CTCs also provides an opportunity for detailed study into why some tumors metastasize or resist treatment.
"Another exciting finding is that the newly identified markers are also expressed in other cancer types, suggesting that this strategy could improve CTC detection across multiple cancers," Cheng said.
Baylor College of Medicine has filed a provisional patent related to this enhanced detection method for circulating tumor cells in triple negative breast cancer.
Other contributors include Khushali J. Patel, Brendan Panici, Ping Gong, Michael T. Lewis and Matthew J. Ellis from Baylor College of Medicine.
Funding was provided by grants from several sources including the Department of Defense (HT94252310753), National Institutes of Health (R01CA276432), CPRIT Cancer Research fellowship (RR160009), CPRIT Core Facility Award (RP220646), P30 Cancer Center Support Grant (NCI-CA125123), CPRIT Core Facility Support Award (CPRIT-RP180672), and NIH grant S10 RR024574.
