Mitochondrial Dysfunction and mtDNA Mutations in Canine Hemangiosarcoma: Novel Biomarkers for Early Diagnosis and Personalized Therapy

SUMMARY: Researchers will study whether mitochondrial dysfunction drives tumor aggressiveness.

THE PROBLEM: Hemangiosarcoma (HSA) is a highly aggressive and rapidly progressing cancer of dogs. Most cases are diagnosed when the tumor is already in an advanced stage. Nearly 90% of all dogs die within the first year of diagnosis, and long-term survival is rare. New treatments are desperately needed.

THE PROJECT: Recent findings in human oncology strongly indicate that mitochondrial dysfunction serves as a crucial driver of cancer progression, metastasis and treatment resistance. Little is known about how mitochondrial dysfunction affects cancer progression in dogs. This innovative study aims to address this critical gap by investigating mitochondrial dysfunction and associated mitochondrial DNA (mtDNA) mutations within canine HSA tumors. The team will use advanced tools such as spatial transcriptomics, mtDNA sequencing and bioenergetic profiling to identify regions of tumors exhibiting severe mitochondrial impairment and hyperactivation. Identifying region-specific mitochondrial dysfunction is vital, as it reveals different metabolic and genetic signatures directly linked to tumor aggressiveness. The team hypothesizes that region-specific mitochondrial dysfunction drives tumor aggressiveness through oxidative stress, mtDNA mutations and synergy with oncogenic mutations.

POTENTIAL IMPACT: Identifying mitochondrial signatures could enable blood-based biomarkers for early detection and personalized therapy.