The causes of cancer revisited: Mitochondrial malignancy and ROS-induced oncogenic transformation - Why mitochondria are targets for cancer therapy

The role of oncoproteins and tumor suppressor proteins in promoting the malignant transformation of mammalian cells by affecting properties such as proliferative signalling, cell cycle regulation and altered adhesion is well established. Chemicals, viruses and radiation are also generally accepted as agents that commonly induce mutations in the genes encoding these cancer-causing proteins, thereby giving rise to cancer. However, more recent evidence indicates the importance of two additional key factors imposed on proliferating cells that are involved in transformation to malignancy and these are hypoxia and/or stressful conditions of nutrient deprivation (e.g. lack of glucose). These two additional triggers can initiate and promote the process of malignant transformation when a low percentage of cells overcome and escape cellular senescence. It is becoming apparent that hypoxia causes the progressive elevation in mitochondrial ROS production (chronic ROS) which