A2B Adenosine Receptor as a novel target in cancer immunotherapy: Validation and optimization of new ligands

Abstract

This doctoral thesis focuses on the study of purinergic signaling in cancer, specifically targeting adenosine receptors. The main objective is the development of potent and selective nonxanthine- based antagonists for adenosine A2B receptors, with potential applications in cancer-targeted therapies. Molecular design strategies, synthesis, biological evaluation, structureactivity relationships, enantiospecific recognition and molecular modeling are explored. To the end, a rational method for dual A2A/A2B antagonists were obtained. The optimization and preclinical validation of new ligands for cancer (immuno)therapy are investigated, revealing promising data in terms of pharmacokinetics and pharmacodynamics.