Synthetic biology-driven innovations in triple-negative breast cancer: Integrating engineering design with targeted therapeutics.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with limited therapeutic options and poor clinical outcomes due to the absence of hormone-responsive receptors. The advent of synthetic biology, which integrates molecular biology with engineering design principles, has introduced new opportunities to develop precise and programmable therapeutic and diagnostic strategies for TNBC. Engineered immune cells, such as chimeric antigen receptor (CAR)-T constructs, can selectively recognize tumor-associated antigens and overcome immunosuppressive barriers. Synthetic gene circuits and engineered bacteria enable tumor-specific delivery of cytotoxic or immunomodulatory agents, while induced pluripotent stem cells (iPSCs) provide patient-specific platforms for disease modeling and drug screening. In parallel, CRISPR/Cas-based genome editing facilitates targeted modulation of oncogenic and tumor-suppressor networks, offering both mechanistic insights and therapeutic innovation. This review highlights current advances in synthetic biology-driven approaches for TNBC, encompassing cell-based, microbial, and nucleic acid-engineered systems. It also discusses their synergistic potential to mitigate tumor heterogeneity, enhance therapeutic specificity, and overcome drug resistance. Collectively, the intersection of synthetic biology, immuno-oncology, and precision medicine holds significant promise for next-generation, adaptive, and patient-tailored treatments for TNBC.