Novel aptamers selected on live cells for specific recognition of triple-negative breast cancer

Triple-negative breast cancer (TNBC), which lacks the expression of oestrogen, progesterone and HER2 receptors, is a high heterogeneous group of tumours with a distinctly aggressive nature and high rates of relapse. Only two targeted therapies have very recently been approved for some women with TNBC thus the identification of further actionable molecular targets is urgently needed. Novel aptamer-based targeted therapies may overcome obstacles of cytotoxic chemotherapy, the mainstay for TNBC treatment. Here, by integrating a cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) method for the specific recognition of TNBC cells with high-throughput sequencing technology, we identified a panel of nuclease-resistant RNA aptamers that bind to human TNBC cell lines, covering different TNBC subtypes, and distinguish them from both normal cells and non-TNBC breast cancer cells. Noteworthy, the aptamers bind to chemo-resistant TNBC cells and differentiate TNBC human samples when used for staining histological tissue sections. Also, they inhibit the mammosphere-forming ability of mesenchymal TNBC cell lines, indicating that their targets are crucial biomarkers for the malignant phenotype. In summary, we report a cell-based selection that enabled, for the first time, the identification of TNBC-specific aptamers and provide innovative data to support their development for assessing the phenotypic diversity underlying tumour progression and response to therapy, which ultimately might improve drug development.