title: Targeting cancer-derived adenosine: new therapeutic approaches.
abstract: CD73 generation of immunosuppressive adenosine within the hypoxic tumor microenvironment causes dysregulation of immune cell infiltrates, resulting in tumor progression, metastases, and poor disease outcomes. Therapies targeted toward the adenosinergic pathway, such as antibodies targeting CD73 and CD39, have proven efficacy in mouse tumor models; however, humanized versions are only in preliminary development. In contrast, A(2A) adenosine receptor antagonists have progressed to late-stage clinical trials in Parkinson disease, yet evidence of their role in oncology is limited. This review will compare the merits and challenges of these therapeutic approaches, identifying tumor indications and combinations that may be fruitful as they progress to the clinic.
  
  
  CONCLUSIONS
  High concentrations of immunosuppressive adenosine have been reported in cancers, and adenosine is implicated in the growth of tumors. This brief review delineates the current treatment strategies and tumor subtypes that will benefit from targeting adenosinergic pathways, alone or in combination with contemporary approaches to cancer treatment.
authors.affiliation: QIMR Berghofer Medical Research Institute; School of Medicine, University of Queensland, Herston, Queensland, Australia; and.
authors.forename: Arabella
authors.initials: A
authors.lastname: Young
authors.affiliation: QIMR Berghofer Medical Research Institute; School of Medicine, University of Queensland, Herston, Queensland, Australia; and.
authors.forename: Deepak
authors.initials: D
authors.lastname: Mittal
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Faculté de Pharmacie et Institut du Cancer de Montréal, Montréal, Québec, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Stagg
authors.affiliation: QIMR Berghofer Medical Research Institute; School of Medicine, University of Queensland, Herston, Queensland, Australia; and mark.smyth@qimrberghofer.edu.au.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000276:immunology*; D000241:Adenosine / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001081:Apyrase / Q000037:antagonists & inhibitors / Q000276:immunology; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D058915:Purinergic P1 Receptor Antagonists
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D007166:Immunosuppressive Agents; D058915:Purinergic P1 Receptor Antagonists; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine