Antiglycolytic strategies in cancer therapy: study of molecules interfering with the altered cancer cell metabolism.

Although the number of cancer hallmarks is increasing with the progressive understanding of molecular pathways involved in tumors, the origin of cancer is still unclear, thus representing a challenging field for researchers. One of the main hallmarks of cancer is represented by an altered metabolism of neoplastic cells, also known as the "Warburg effect", in which energy production is mainly shifted from oxidative phosphorylation (OXPHOS) to an increased rate of glycolysis. This feature correlates with malignant tumors and poor prognosis. My PhD was focused on the design and synthesis of new compounds, which can interfere with the altered metabolism of cancer cells by targeting the "Warburg effect" at different levels. In particular, our attention was focused on two of the main glycolytic targets, the LDH-5 enzyme and the glucose transporter GLUT-1, which were found to be overexpressed in several malignant tumors. Then, the third target investigated is estrogen receptor beta (ERβ), which was recently found to correlate with cancer cell metabolism, and part of my thesis was dedicated to the synthesis of new ketoxime-based compounds as ERβ selective agonists.