Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function

Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function

KRAS is an an oncogene which is found to be upregulated in many cancers. In pancreatic ductile carcinoma, KRAS mutations are known to be a driver mutation in tumorigenesis. The authors use an inducible mouse model of mutated KRAS, where the mutation is a loss of function. They show that, after KRAS ablation, a small set of surviving cancer cells persist. These are metabolically different to prototypical cancer cells, as they are addicted to OXPHOS whereas tumour cells tend to be addicted to glycolysis. The authors hypothesize that the mitochondrial hyperpolarization of these cells causes them to have a higher threshold for activating the mitochondrial permeability transition pore, which induces cell death. They find that inhibiting OXPHOS can eliminate the survivor cells.