Perspectives on the use of flavonoids in glioblastoma treatment by targeting adenosine receptors

Flavonoids are a large class of natural polyphenolic substances ubiquitously synthesized in the plant kingdom. When entering the human body, these compounds can exert a wide range of biological activities, including immunomodulatory, antiinflammatory, and anticancer effects. Over the recent years, the mechanisms underlying these actions have become increasingly clear, also indicating the important involvement of G protein-coupled receptors (GPCRs), such as adenosine receptors, in signal transduction networks. In this perspective article, the potential role of flavonoids as adenosine receptor antagonists on the development, progression, and spread of glioblastoma is discussed, blocking the tumor-promoting and immunosuppressive actions of elevated levels of endogenous adenosine. Therefore, flavonoids can be considered as structural leads for developing novel antiglioblastoma agents, applied either alone or as boosters of chemo- or immunotherapy to improve the quality of life and outcome of patients. The importance of these studies is, in turn, emphasized by the current lack of effective treatment strategies for this highly aggressive and fast-growing brain tumor, associated with poor prognosis.