Aug 2026· Extracellular Vesicles and Circulating Nucleic Acids· Vol 7, pp. 1276-96· 0 citations· 101 references
TL;DR
Targeting this dynamic form of intercellular communication offers a promising therapeutic strategy to overcome tumor metabolic plasticity, immunosuppression, and resistance to therapy.
Abstract
Solid tumors account for the majority of cancer cases, and their incidence continues to increase. A solid tumor is not an isolated mass but interacts dynamically with cells in the tumor microenvironment. Mitochondria, which are essential for energy production and the regulation of apoptosis, play a critical role in cellular function and may serve as therapeutic targets. A growing body of evidence demonstrates that mitochondria can be transferred between cells via extracellular vesicles, tunneling nanotubes, gap junctions, and cell fusion. This process across various cell types, including stromal cells, immune cells, and cancer cells, and is enhanced under stress conditions, such as hypoxia and chemotherapy. Under these conditions, mitochondrial transfer enables tumor cells to acquire functional mitochondria from neighboring cells, thereby enhancing their metabolic plasticity and survival capacity. Mitochondrial transfer thus represents a critical adaptive mechanism that supports tumor progression. Targeting this dynamic form of intercellular communication offers a promising therapeutic strategy to overcome tumor metabolic plasticity, immunosuppression, and resistance to therapy.
It is proposed that mitochondrial transfer acts as a tripartite educator during metastasis by driving three coordinated programs: metabolic licensing, immune rewiring, and stromal remodeling.
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