Bioactive Natural Compounds in Triple-Negative Breast Cancer: Molecular Targets and Therapeutic Perspectives

Abstract

Triple-negative breast cancer represents one of the most aggressive and therapeutically challenging subtypes of breast malignancies, characterized by marked biological heterogeneity, rapid progression, and limited targeted treatment options. Conventional therapies are frequently constrained by drug resistance, systemic toxicity, and high rates of recurrence. In this context, natural products have gained increasing attention as multifunctional agents capable of modulating several hallmarks of triple-negative breast cancer. Bioactive compounds, including polyphenols, terpenoids, alkaloids, and marine-derived molecules, exhibit pleiotropic antitumor effects by interfering with key oncogenic pathways. Importantly, these compounds have demonstrated the ability to counteract major mechanisms of therapeutic resistance, modulate the tumor immune microenvironment, and enhance the efficacy of standard chemotherapy and immunotherapy. Advances in drug delivery strategies, such as nanoparticle-based systems and tumor-targeted formulations, together with patient-specific molecular profiling, further expand the potential of these agents within personalized treatment approaches. This narrative review critically examines the role of natural compounds in targeting the hallmarks of triple-negative breast cancer and their potential synergistic use to improve therapeutic efficacy while reducing treatment-related toxicity. Overall, the integration of natural product-based strategies into precision oncology frameworks may offer more effective, less toxic, and individualized therapeutic options for this aggressive breast cancer subtype.