Recent reports including ours demonstrated metformin together with chemotherapeutic agents induced a pronounced cytotoxic effect.3 Metformin although it reduced cancer risk and improved prognosis in several cancers, the outcomes were relatively heterogeneous since high-dose metformin is challenging to achieve without severe side effects in patients.4 Thus therapeutic exploitation of the PEN2-ATP6AP1 axis together with metformin alternatives and neoadjuvant chemotherapies respectively might promise an improved outcome in T2D and cancer patients. This evidence concerns the gene PSENEN and cancer.