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Surface Marker Identification to Capture Live Circulating Tumor Cells in Metastatic Triple-Negative Breast Cancer
Bree M Lege1,2, Khushali J Patel1,2, Brendan Panici1,2
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Cancer Research Communications
|January 16, 2026
Summary
Researchers identified new surface markers to improve the detection of rare circulating tumor cells (CTCs) in aggressive triple-negative breast cancer (TNBC). This enhances live CTC capture for better monitoring and targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Metastatic triple-negative breast cancer (TNBC) is aggressive with limited targeted treatments.
- Circulating tumor cells (CTCs) are crucial for monitoring metastasis and treatment response but are rare and heterogeneous.
- Existing CTC markers poorly detect mesenchymal TNBC cells, hindering live capture and RNA quality for analysis.
Purpose of the Study:
- To develop an enhanced workflow for live capture and single-cell RNA sequencing (scRNA-seq) of TNBC CTCs.
- To identify novel surface markers for improved detection of diverse CTC populations, including mesenchymal TNBC cells.
- To increase the sensitivity and coverage of CTC detection for comprehensive metastatic breast cancer research.
Main Methods:
- Developed a workflow for live CTC capture and scRNA-seq.
- Utilized a mouse model of metastatic TNBC to identify new CTC surface markers (AHNAK2, CAVIN1, ODR4, TRIML2).
- Validated new markers in combination with traditional markers in mouse models and patient samples.
Main Results:
- Identified four novel CTC surface markers (AHNAK2, CAVIN1, ODR4, TRIML2) specific to TNBC cells.
- Combining new markers significantly improved CTC detection rates in TNBC models and patient samples.
- The integrated marker approach achieved highest CTC coverage, enabling diverse population identification and preserving RNA for scRNA-seq.
Conclusions:
- The novel markers enhance detection and live capture of TNBC CTCs, including mesenchymal subtypes.
- This approach facilitates comprehensive analysis of CTC heterogeneity via scRNA-seq.
- Improved CTC detection and live capture pave the way for advanced liquid biopsy applications in metastatic breast cancer management.
