HPSE and pancreatic neoplasm: Moreover, as the recent attempts to translate direct targeting of AKT pathway into clinic were proven to be highly challenging (He et al., 2021), heparanase-inhibiting approaches [which are currently under active development (Rivara et al., 2016; He et al., 2022)] may offer an appealing tactic to sensitize pancreatic tumors to gemcitabine, as well as uncouple PDAC and diabetes cancer progression in a significant fraction of patients.