Mitochondrial dynamics: A promising tool for personalized TNBC management.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic form of breast cancer and is associated with poor prognosis due to the lack of targeted therapies. Mitochondrial dysfunction is a crucial factor contributing to tumor growth and chemoresistance in TNBC. Dysregulation in mitochondrial dynamics leads to disruption of the normal process of oxidative phosphorylation, elevated reactive oxygen species generation, and resistance to apoptosis, contributing to TNBC aggressiveness. Moreover, alterations in mitochondrial energetics, including elevated glycolysis and glutamine addiction, provide metabolic advantages for TNBC growth and survival. Emerging therapeutic strategies targeting mitochondrial vulnerabilities have shown potential for TNBC management. Inhibitors targeting mitochondrial dynamics, including Mdivi-1, dynasore, and cepharanthine, act by restoring mitochondrial homeostasis and impairing excessive fission to stimulate apoptosis. Mitochondrial energetics inhibitors, such as 2DG, 3BP, clotrimazole, and etomoxir, disrupt mitochondrial metabolic processes and reduce tumor growth in TNBC. This review highlights the latest advancements in mitochondrial dynamics and energetics in TNBC and explores the molecular mechanisms underlying their dysregulation. It also explores the therapeutic potential of targeting mitochondrial function for personalized strategies leading to improved clinical management of TNBC.