Purinergic Signaling as a Therapeutic Target for Cancer and Inflammation-Related Diseases: Insight from Biological Mechanisms to Therapeutic Translation

Purines and their derivatives-mainly adenosine triphosphate (ATP) and adenosine-serve as core regulators of intracellular energy homeostasis and nucleotide biosynthesis in mammalian cells. Beyond their metabolic functions, these molecules act as endogenous ligands to bind to membrane-embedded purinergic receptors, triggering downstream signaling cascades that orchestrate extracellular communication, known as "purinergic signaling" pathway. The purinergic signaling network encompasses purine ligands (mainly ATP, ADP, AMP, adenosine), ectonucleotidases (CD39, CD73), and purinergic receptors classified into P1, P2X and P2Y subfamilies. Purinergic signaling is intricately integrated with other neurotransmitter and signaling networks, coordinating fundamental cellular behaviors including proliferation, differentiation, migration, and apoptosis-processes critical for maintaining organismal homeostasis. Dysregulation of this pathway is etiologically linked to a broad spectrum of pathologies, such as neurodegenerative disorders, rheumatic autoimmune diseases, chronic inflammation, and malignancies. Against this backdrop, there is a surging interest in further elucidating the multifaceted roles of purinergic signaling in inflammatory and immune responses.Given purines’ crucial role in foundational metabolic processes and physiological regulation, dysfunction of the purine/purinergic receptor system drives pathological remodeling in conditions ranging from metabolic diseases such as diabetes and obesity to autoimmune diseases and cancer. To date, a growing arsenal of therapeutics targeting purine metabolism or purinergic receptors has been developed, particularly in the context of inflammation and immunity-fields where purinergic receptors have emerged as key mediators of damage-associated molecular pattern (DAMP) responses (e.g., ATP release during tissue injury). While progress has been made in targeting this pathway, critical knowledge gaps remain regarding the functional crosstalk between purinergic components, their tissue-specific roles, and their contributions to disease pathogenesis. Resolving these gaps is prerequisite to the widespread clinical application of purine-based therapeutic strategies. In summary, purinergic signal transduction represents a complex and understudied system with many of its functions remain to be uncovered. This special issue seeks to serve as a comprehensive resource for purine researchers and immunologists by compiling key advances in understanding purinergic signal transduction in inflammation and immunity.In this research topic, our primary objective is to convene scholars engaged in investigations of diverse components within the purine signaling system and deliver a state-of-the-art synthesis of its functional implications in inflammation-associated disorders and malignancies. We extend a cordial invitation for submissions encompassing original research, review papers, perspectives, clinical trials, and case reports, which may address (but are not restricted to) the following thematic areas:1. Novel molecular mechanisms of purinergic signaling in cancer biology2. Regulation of innate and adaptive immunity by the purinergic axis during tumour progression3. Purinergic pathway contributions to chronic inflammation, autoimmune disorders, and transplant immunology4. Molecular pharmacology of purine compounds, ectonucleotidases, and purinergic receptors as therapeutic targets5. Clinical trials, biomarkers, and translational research bridging preclinical findings with oncology and inflammation indications Topic editors: Long Wu, Anna Lisa Giuliani, Fabio Malavasi Source: https://www.frontiersin.org/research-topics/85382/purinergic-signaling-as-a-therapeutic-target-for-cancer-and-inflammation-related-diseases-insight-from-biological-mechanisms-to-therapeutic-translation