Research Progress on Chinese Medicine Derived Bioactive Monomers in Breast Cancer Resistance and Programmed Cell Death

Abstract

Therapeutic responses in breast cancer are jointly shaped by molecular subtype, clonal evolution, and the tumor microenvironment. Endocrine therapy, chemotherapy, radiotherapy, and targeted therapy can all select for acquired resistance. Bioactive monomers derived from Chinese medicinal materials have defined chemical structures and frequently act on interconnected signaling networks. They may influence drug efflux, epithelial-mesenchymal transition, tumor stemness, and cell-death thresholds by modulating PI3K/AKT/mTOR, MAPK, NF-kappaB, AMPK/HIF-1alpha, and Wnt/beta-catenin signaling. This review evaluates representative compounds, including curcumin, shikonin, baicalin, baicalein, berberine, resveratrol, tanshinone IIA, and dihydroartemisinin, with emphasis on apoptosis, ferroptosis, necroptosis, autophagy-related processes, and restoration of treatment sensitivity. It further examines microenvironmental barriers formed by hypoxia, cancer-associated fibroblasts, tumor-associated macrophages, regulatory T cells, and immune checkpoints. Preclinical studies of shikonin-induced immunogenic cell death, berberine-mediated GSDME pyroptosis, and natural-polyphenol combinations that reshape immune infiltration provide a mechanistic bridge to immunotherapy; however, they do not establish these compounds as substitutes for, or routine partners of, immune-checkpoint inhibitors. Most evidence derives from cell lines and animal models, and opposite effects may occur with different doses, formulations, or treatment schedules. Future work should establish target causality in subtype-defined patient-derived models, quantify pharmacologic synergy, match experimental exposure to achievable human exposure, and use rigorously designed clinical trials to define the population likely to benefit and the boundaries of safety