By Ana Espino | Published on October 21, 2025 | 4 min readTriple-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
mernovative 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.
Read next: Trastuzumab Deruxtecan: a new hope for HER2-mutated triple-negative breast cancers without HER2 expression
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.
Read next: Triple blow, triple clinical challenge
About the author – Ana EspinoPhD in Immunology, specialized in Virology
