Targeting Survivin in breast cancer involves molecular mechanisms, clinical translation challenges, and emerging strategies

Survivin (BIRC5), a member of the inhibitor of apoptosis proteins family, is aberrantly activated in tumors, and is involved in tumor growth, treatment resistance and poor prognosis. This review summarizes the molecular mechanisms, expression heterogeneity, prognostic value, and therapeutic strategies targeting Survivin in breast cancer, with a critical focus on the major barriers to clinical translation and emerging directions to overcome them. Survivin exerts anti‑apoptotic effects and serves as a core component of the chromosomal passenger complex to drive cell proliferation. In addition, Survivin contributes to tumor angiogenesis, chemotherapy resistance, and cancer stemness. Its expression shows marked heterogeneity across breast cancer subtypes. Current Survivin‑targeted strategies include gene silencing technology, small‑molecule inhibitors, dominant‑negative mutants, peptide vaccines, and nanocarrier‑based delivery systems. However, clinical trials have revealed several persistent barriers. Indirect inhibition triggers compensatory upregulation, while Survivin lacks a druggable pocket for small‑molecule inhibitors. Delivery remains inefficient, and off‑target toxicity limits the therapeutic application. To address these challenges, emerging directions focus on epigenetic regulation, direct protein degradation, advanced delivery technologies, synergistic sensitization, and computational approaches for patient stratification. Based on available evidence, we propose several clinical translation takeaways to benefit from Survivin‑based therapies. Survivin‑targeted therapies should be positioned as complementary sensitizers to chemotherapy, immunotherapy, or PARP inhibitors, rather than as monotherapy replacements. However, most of these strategies remain preclinical, and prospective biomarker-driven trials are needed to establish clinical utility. In conclusion, Survivin remains a mechanistically attractive target in breast cancer. Its eventual clinical application will depend on overcoming delivery, toxicity, and patient-selection challenges through rationally designed combination strategies and rigorous clinical evaluation. Survivin promotes breast cancer progression via multiple mechanisms. Expression of Survivin varies across breast cancer subtypes. Most clinical-stage Survivin-directed agents have failed to demonstrate efficacy. Clinical translation of Survivin-targeted therapies requires biomarker-driven patient selection and rigorous clinical validation.