Mitochondrial markers for prostate cancer prognosis and therapy
Mitochondria are crucial organelles for energy production, apoptosis and intracellular production of reactive oxygen species (ROS). A shift in cellular energy production from oxidative phosphorylation in mitochondria to anaerobic glycolysis is a fundamental property of cancer cells. Due to the essential role of enzymes encoded by the mitochondrial DNA (mtDNA) in energy metabolism, alterations of the mtDNA have been suspected to be able to cause a metabolic shift in tumors. Because mitochondria play important roles in both ROS production and apoptosis, the conclusion that they could influence the occurrence and especially the progression of cancer is obvious. There is accumulating evidence of a role of mitochondria in different tumor types, among them prostate cancer.
The exploitation of alterations of mitochondrial function and genome during prostate cancer development and progression is expected to uncover surrogate markers that will result in new diagnostic procedures; in addition, the identification of mitochondrial targets could lead to the development of new drugs for prevention and treatment.
Our recent study on mtDNA mutations in prostate cancer revealed 41 somatic mutations in 22 out of 30 patients . The presence of somatic mutations in transfer RNAs (tRNAs) was found to be associated with elevated PSA levels. The level and degree of heteroplasmy increased with increasing tumor grade. Mutations in mitochondrial tRNAs, ribosomal RNAs or protein coding genes might impair mitochondrial function and promote a shift towards increased anaerobic glycolysis.
- Information on the role of mitochondria in tumor development, progression, therapy resistance.
- Mitochondrial markers for prostate cancer to be used in diagnosis, prognosis and risk assessment and selection of therapy. Surrogate markers for mitochondrial function and energy metabolism.
- Putative mitochondrial therapy targets.
Oncotyrol - Center for Personalized Cancer Medicine GmbH
Division of Genetic Epidemiology, Innsbruck Medical University
Department of Urology, Innsbruck Medical University
OROBOROS Instruments GmbH, Innsbruck
Theracode GmbH, Mainz
2012-07-01 to 2015-06-30
FFG (State) funding: € 222.222,22 Basis of assessment of the fundable costs: € 444.444,44