SIRT1 and Cowden syndrome 1: The review provides an overview of the current in vitro and in vivo CS models, discusses their advantages and limitations, and highlights the recent efforts in the development of new targeted therapies against CS dependencies, including IDH1/2 mutations, NAD+ dependency, and SIRT1-HIF-2α axis, or exploring DR5 targeting, antiangiogenic therapies, epigenetic drugs, and immunological approaches.