Research seminars Driving out a tumor driver: dislodging Hexokinase 2 from mitochondria/ER contact sites to kill neoplastic cells

Hexokinase 2 (HK2) is a metabolic enzyme overexpressed by the majority of neoplastic cells. HK2 resides in mitochondria/ER contact sites (MAM) of tumor cells where it exerts a potent antiapoptotic function. Indeed, HK2 expression is associated to treatment resistance and worst prognosis in patients. In parallel, its genetic ablation in mice bearing tumors is curative. As a consequence, HK2 is a promising target for an antineoplastic therapy. For this reason, we designed and tested an innovative and translatable trojan horse approach that dislodges HK2 from MAMs, rapidly induces mitochondrial Ca²⁺ overload and triggers tumor cell death in different models.