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<p>Breast cancer is a heterogeneous disease affecting women globally. Despite significant advancements in therapeutic interventions in recent years, breast cancer remains a leading cause of cancer-related morbidity in women. Breast cancer’s diverse molecular subtypes and escalating complexities in targeted therapies underscore the imperative need to explore novel therapeutic targets. The obstruction of apoptosis and the suppression of cell death are hallmarks of malignant tumors. Cell death, a pivotal regulatory event during tumorigenesis, includes apoptosis, anoikis, autophagy, necroptosis, ferroptosis, pyroptosis, and cuproptosis. This review systematically dissects the molecular underpinnings of cell death pathways in breast cancer, offering novel mechanistic insights and therapeutic opportunities to inform clinical management strategies.</p> Graphical Abstract <p>Breast cancer is characterized by inter- and intra-tumoral heterogeneity across intrinsic subtypes (Luminal A/B, HER2-positive, TNBC) and cellular subpopulations. This heterogeneity creates exploitable vulnerabilities in regulated cell-death programs, encompassing apoptosis, anoikis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis. A compelling translational example is the inhibition of GSTP1, which not only triggers ferroptosis but also potentiates antitumor immunity through DC activation and enhanced CD8⁺ T-cell responses. Overall, mapping heterogeneity to specific death pathways supports mechanism-guided patient stratification and combination therapy design.</p> <p></p>

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Distinct mechanisms of cell in breast cancer and their clinical implication

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月9日

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  • Aodi Li,
  • Sishi Liu,
  • Ying Xuan,
  • Ying Liang,
  • Lei Wang,
  • Lei Zhao

摘要

Breast cancer is a heterogeneous disease affecting women globally. Despite significant advancements in therapeutic interventions in recent years, breast cancer remains a leading cause of cancer-related morbidity in women. Breast cancer’s diverse molecular subtypes and escalating complexities in targeted therapies underscore the imperative need to explore novel therapeutic targets. The obstruction of apoptosis and the suppression of cell death are hallmarks of malignant tumors. Cell death, a pivotal regulatory event during tumorigenesis, includes apoptosis, anoikis, autophagy, necroptosis, ferroptosis, pyroptosis, and cuproptosis. This review systematically dissects the molecular underpinnings of cell death pathways in breast cancer, offering novel mechanistic insights and therapeutic opportunities to inform clinical management strategies.

Graphical Abstract

Breast cancer is characterized by inter- and intra-tumoral heterogeneity across intrinsic subtypes (Luminal A/B, HER2-positive, TNBC) and cellular subpopulations. This heterogeneity creates exploitable vulnerabilities in regulated cell-death programs, encompassing apoptosis, anoikis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis. A compelling translational example is the inhibition of GSTP1, which not only triggers ferroptosis but also potentiates antitumor immunity through DC activation and enhanced CD8⁺ T-cell responses. Overall, mapping heterogeneity to specific death pathways supports mechanism-guided patient stratification and combination therapy design.