Triple negative breast cancer, (TNBC) comprises between 10 and 15% of all breast cancer cases [1], and 40% of all TNBC patients endure recurrence [2]. This amounts to 4% of all breast cancer patients enduring TNBC more than once. Recurrences can be treated much more safely and easily if they are caught early enough, but unfortunately, testing for recurrence is uncomfortable, lengthy, inconvenient, and expensive. Our project is an attempt to solve this issue: we are developing an easy to use, effective, at-home blood test for TNBC recurrence. This test relies on a small detail of TNBC: it increases the concentration of two miRNAs in the blood, miRNA21 and miRNA155 [3]. For our project, we have engineered a molecular sensor for these miRNAs, called a toehold switch, which reacts to the presence of these specific microRNAs and triggers the expression of a reporter gene. To reduce false positive signals, this toehold is designed as an AND gate, only triggering expression when both microRNA biomarkers are present. To enable detection as early as possible, we envision this being an at-home test, so we also have helped to develop an inexpensive fluorescence sensor that can be used to measure expression of a GFP reporter. Together, these measures can ultimately be refined to create an inexpensive, effective, and simple at-home test for TNBC recurrence.
1]Zagami P, Carey LA. Triple negative breast cancer: Pitfalls and progress. NPJ Breast Cancer. 2022 Aug 20;8(1):95. doi: 10.1038/s41523-022-00468-0
[2]Stewart RL, Updike KL, Factor RE, Henry NL, Boucher KM, Bernard PS, Varley KE. A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer. Cancer Res. 2019 Jul 1;79(13):3466-3478. doi: 10.1158/0008-5472.CAN-18-3014
[3]Tang Q, Ouyang H, He D, Yu C, Tang G. MicroRNA-based potential diagnostic, prognostic and therapeutic applications in triple-negative breast cancer. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2800-2809. doi: 10.1080/21691401.2019