TNBC: could everything be happening in the mitochondria?

By Ana Espino | Published on october 21, 2025 | 3 min read


Triple-negative breast cancer (TNBC) is a particularly aggressive form of cancer, characterized by the absence of hormone receptors (ER/PR) and HER2. It primarily affects younger women, progresses rapidly, and carries a high risk of relapse, especially due to the lack of exploitable therapeutic targets. Currently, chemotherapy remains the standard treatment, but it has major limitations: variable efficacy, significant toxicity, and frequent development of resistance. In light of this therapeutic dead end, mechanisms of mitochondrial quality control — such as fission, fusion, mitophagy, and biogenesis — are emerging as promising new areas of exploration. These processes, essential for cell survival, are often hijacked by tumor cells to resist stress and sustain their growth. Within this context, the study was designed to explore how mitochondrial quality control is altered in triple-negative breast cancer (TNBC) and to assess its potential as an innovative therapeutic target.   Sabotaging the mitochondria: the key to slowing tumor growth? The article provides an in-depth analysis of mitochondrial quality control mechanisms and their specific alterations in triple-negative breast cancer (TNBC). It highlights a marked dysregulation of mitochondrial dynamics, characterized by increased fission, reduced fusion, and impaired mitophagy. These imbalances promote tumor cell survival, proliferation, and migration in a hostile environment. Several key proteins are involved in these processes: DRP1 for fission, MFN1/MFN2 for fusion, PINK1/Parkin for mitophagy, and PGC1α for biogenesis. In TNBC, these components are often overexpressed or hijacked, allowing cancer cells to resist oxidative stress and maintain their energy metabolism. Several experimental therapeutic agents targeting these pathways have shown promising results — including fission inhibitors such as Mdivi-1, mitophagy inducers, and modulators of mitochondrial biogenesis. These approaches open the door to new targeted strategies, which still need to be validated clinically.   A new energy pathway against cancer? Triple-negative breast cancer remains one of the most aggressive and difficult types to treat due to the absence of specific therapeutic targets. The main challenge lies in developing effective treatments capable of overcoming tumor resistance while limiting systemic toxicity. This study aimed to investigate the role of mitochondrial alterations in TNBC and to evaluate their potential as therapeutic targets. It highlights significant dysregulation in the processes of fission, fusion, mitophagy, and biogenesis, all of which contribute to tumor cell survival. However, limitations of the study remain and justify further research. Future work should include clinical studies to validate the identified targets, development of more specific and less toxic mitochondrial modulators, and a deeper understanding of tumor metabolic interactions. Ultimately, combining mitochondrial biology with precision medicine could pave the way for personalized therapeutic strategies for patients with TNBC.  

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About the author – Ana Espino
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.