Researchers identify mitochondrial metabolic pathways in cancer resistance

New research has identified specific mitochondrial metabolic processes that contribute to cancer progression and treatment resistance in both breast and prostate cancers.

In triple-negative breast cancer (TNBC), studies have identified the mitochondrial enzyme α-aminoadipate aminotransferase (AADAT) as a metabolic immune checkpoint. High expression of AADAT is linked to reduced CD8+ T-cell density and poorer survival rates. Genetic silencing of AADAT in murine models was shown to curtail tumor growth and metastasis by enhancing T-cell activation and sensitizing tumors to PD-1/CTLA-4 blockade. This process involves the regulation of malate levels and CoQ10 biosynthesis.

In prostate cancer research, investigations into radioresistant tumors revealed increased mitochondrial biogenesis and altered metabolism. Using the compound AuPhos-89, which targets mitochondria to increase reactive oxygen species and disrupt ATP synthesis, researchers were able to reduce tumor growth in immunocompetent mice. Combining this mitochondrial targeting with radiotherapy proved more effective than either treatment alone, even under hypoxic conditions.