Cellular & molecular biology lettersOct 2, 2025

Planned cell death in triple-negative breast cancer

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 19, 2026

Abstract

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression.

The lack of actionable molecular targets in TNBC contributes to its resistance to conventional treatments.
Several programmed cell death (PCD) pathways, including and autophagy, are involved in TNBC pathogenesis and treatment.
An integrated network of PCD pathways may offer opportunities for novel targeted interventions.
Modulation of one PCD pathway could influence others, potentially enhancing therapeutic effectiveness.
The interplay between PCD pathways and immunotherapy outcomes may support the development of synergistic treatment approaches.
Challenges remain due to tumor diversity and discrepancies between preclinical models and human physiology.

Simplified

Triple-negative breast cancer (TNBC) is a particularly aggressive and therapeutically challenging subtype of breast cancer, defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. This absence of actionable molecular targets contributes to its resistance to conventional treatments. This review provides an overview of the mechanistic functions, interrelated processes, and therapeutic implications of several programmed cell death (PCD) pathways-including , pyroptosis, necroptosis, autophagy, and -in the context of TNBC pathogenesis and treatment. A conceptual framework is proposed for leveraging these interconnected cell death pathways as a basis for novel targeted interventions. Given the complex interplay among various PCD forms characterized by shared features such as inflammation, mitochondrial dysfunction, and overlapping molecular mediators, this integrated network offers promising opportunities for combinatorial therapeutic strategies. Modulation of one cell death pathway may influence others, potentially amplifying therapeutic efficacy. Furthermore, these PCD pathways are highly relevant to immunotherapy outcomes, offering a foundation for synergistic treatment modalities. This review provides an in-depth analysis of the crosstalk between immune-based therapies and PCD, along with a comprehensive discussion of derived therapeutic approaches. However, tumor diversity, resistance mechanisms, and discrepancies between preclinical models and human physiology pose major challenges in applying these findings clinically. The overarching goal is to present innovative insights and strategies to enhance the clinical management of TNBC and ultimately improve patient outcomes.

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Declarations. Ethics approval and consent to participate: Since this article does not pertain to research involving humans or animals, the review and/or approval of an ethics committee is not required. Competing interests: The authors declare that they have no known competing financial interests or personal relationships.

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Planned cell death in triple-negative breast cancer

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