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Life sciences · Journal article
Theoretical and Natural Science · October 20, 2026
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Breast cancer is a malignant tumor with a high incidence in the world. The treatment of breast cancer is faced with the dual dilemma of unavailability of molecular targets and chemotherapy resistance. New intervention strategies are urgently needed. Small interfering RNA (siRNA) therapeutic drugs have the ability for sequence-specific gene silencing. These drugs can inhibit key targets such as the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and survivin, as well as the oncogenic transcription factor signal transducer and activator of transcription 6 (STAT6) at the messenger RNA (mRNA) level. This inhibition effectively restores the chemosensitivity of tumor cells and inhibits the malignant phenotype. This effect provides a feasible way to overcome the limitations associated with traditional targeting dependence and drug resistance. The clinical transformation of siRNA is still hampered by two core challenges including low efficiency of in vivo delivery and safety risks. This recognition triggers unexpected toxicity and reduces the therapeutic effect. Current studies have partially alleviated the above-mentioned obstacles through nanocarrier design, chemical modification, and targeted ligand coupling. Nevertheless, sufficient data on long-term administration, in situ tumor models, and systems toxicology are still lacking. The strategy of combined gene silencing or combined therapy remains to be further explored. This review covers key molecular targets, extracellular and intracellular delivery disorders, immune stimulation and target mechanisms. The prospect of multifunctional nanoplatforms and combined therapy is discussed, which provides a theoretical reference for the optimization and clinical transformation of siRNA-based breast cancer therapeutic drugs.