Targeting mitochondria biogenesis with small molecules as a new therapeutic approach in oncology

All our cells need energy to survive. This is generated in sites within cells (organelles) called mitochondria which function as the cell’s powerhouse. When mitochondria are faulty or damaged critical organs like the heart, brain and muscles lack energy and can no longer function leading to severe diseases and eventually death. The process of making new mitochondria (mitochondria biogenesis) is important to maintain a healthy mitochondria balance at all times. Mitochondria biogenesis crucially depends on highly specialised pathways that precisely target 1500 mitochondrial proteins to these organelles. These pathways are therefore just as important as mitochondria function. Some of the deadliest cancers (like pancreatic cancer, predicted to be the second deadliest by 2030) critically depend on mitochondria using them to evade chemotherapy and become resistant. Blocking mitochondria in such therapy-resistant cancers targets their Achilles’ heel providing an efficient strategy to eradicate hard to treat cancers. However, this is still a largely unmet clinical need and remains an unexplored area. In this project we will develop novel small molecule blockers that inhibit specifically a master regulator protein of mitochondria biogenesis. We will build on our unique mechanistic understanding of this pathway using a combination of biochemical/compound screening assays with computational chemistry to develop a novel class mitochondria biogenesis cancer therapeutics.