The rationale of the project is the exploitation of the metabolic differences between normal and tumor cells to achieve selective toxicities in anticancer chemotherapy by targeting essential components of different connected pathways: cell proliferation, glycolysis, and lipid metabolism. We will focus on already validated anticancer macromolecular targets that act in interconnected networks: glucose transporters, metabolic enzymes, cannabinoid receptors, and tyrosine kinases. We will focus on neuroblastoma and glioblastoma tumors that are among the most difficult cancers to treat. Thus, the development of novel chemical entities specifically designed to target the metabolic alterations of these cancers will have an immediate impact on the medical field. Novel chemical entities will be selected through iterative cycles of compound optimization of the pharmacokinetic properties and toxicity. This project brings together five research Units with strong complementary expertise in drug development. Involvement of young scientists at the doctoral and postdoctoral levels, will train a new generation of expert scientists in the field of drug development.