Mitochondrial Targeting Inhibits Breast Cancer Stem Cells: Preclinical Findings

Synopsis

Mitochondria are vital cell components that generate energy, build essential molecules, and support cell signaling. In cancer, mitochondria often adapt to fuel tumor growth by supplying the energy and materials needed for new cell formation. Cancer stem cells (CSCs)—a small but critical cell population—drive chemotherapy resistance, cancer relapse, and metastasis. Unlike most cancer cells that rely on glycolysis for energy, breast CSCs depend heavily on mitochondrial oxidative phosphorylation (OxPhos). This study shows that activating the mitochondrial protease ClpP with specific agonists disrupts mitochondrial function, causing depletion of NAD(P)+ and NAD(P)H, creating redox imbalances, and blocking key pathways important for CSC survival. YAP, Myc, and HIF signaling. Together, these effects strongly inhibit breast CSC growth and self-renewal in both laboratory and animal models, highlighting ClpP agonists as a promising strategy to target therapy-resistant breast CSCs by disturbing mitochondrial balance and critical metabolic pathways.

Journal

Cancer Research Communications