We establish structure activity relationships in both receptor families, in order to provide selective agents as pharmacological probes and potential therapeutic agents. Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892Įxtracellular nucleosides and nucleotides acting at adenosine receptors (ARs) and P2Y receptors (P2YRs), respectively, both G protein-coupled receptors (GPCRs), are important signals to modulate biological processes in many organs and tissues. Structure-based discovery of novel ligands of GPCRs: adenosine and P2Y receptors

Why? Do nucleotides support tumor growth as they support inflammation? Do they modulate responses of inflammatory cells in the tumor interstitium? And the P2 receptors? Do they participate in anti-tumor responses or rather support cancer progression? Does the tumor-bearing host benefit from P2 receptor blockade? And what we know of cancer growth in P2-KO animals? These are currently hot issues that are enormously increasing our understanding of cancer, besides of course purinergic signalling. Investigation of the pleiotropic functions of extracellular nucleotides (and their receptors, the P2 receptors) revealed that they are fundamental constituents of the inflammatory as well as tumor microenvironment. Then, Geoff Burnstock came to show us that purines have a much wider role to play in physiology and pathology than ever thought before. Now, we are still struggling to fully understand the role of inflammation in cancer progression and metastatic spreading, and try to exploit it to the benefit of the patient. As early as 1858 Virchow had clearly suggested that there was a causal link between chronic inflammation and cancer, but we have simply forgotten this crucial observation. The relationship between inflammation and cancer is a paradigmatic example of this. Men are often oblivious of the contributions of our ancestors. The cancer-promoting effect of inflammation was further dissected into its mechanistic components with the discovery of those cells responsible for immunosuppression within the cancer microenvironment, the myeloid-derived suppressor cells (MDSCs). Thousand reports followed ever since highlighting the cancer-promoting effects of inflammation, a finding to be honest that was well known to practicing physicians. This changed dramatically following the seminal observation of Francis Balkwill that TNF-ko mice were surprisingly less prone to cancer than wt. Until recently, it was generally thought that inflammation was a protective response, or in the worst case the epiphenomenon of body reaction to cancer with no relevant consequences.

Inflammation and cancer have a long-standing association. Purinergic receptors in cancer and inflammation: from Rudolph Virchow to Geoff Burnstockĭepartment of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy

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