title: Targeting CD73 and downstream adenosine receptor signaling in triple-negative breast cancer.
abstract: BACKGROUND
  Despite significant improvements in diagnosis and therapy over the past 20 years, breast cancer remains a worldwide public health issue. In particular, triple negative breast cancer (TNBC), a subset of very aggressive breast tumors, is associated with a poor prognosis and has very few efficient therapeutic options. The ectonucleotidase CD73 has recently emerged as a promising new target for TNBC in preclinical models. Pharmacological targeting of CD73 and downstream adenosine A2A/A2B receptor signaling is currently an active field of research that could lead to the development of new cancer therapeutics, including options against TNBC.
  
  
  METHODS
  This article reviews the basic structural and molecular features of CD73 and its role in the development of cancer, with a particular focus on CD73's role in the biology of TNBC.
  
  
  CONCLUSIONS
  It was recently demonstrated that CD73 expression in TNBC is associated with worse clinical outcomes and increased resistance to anthracycline chemotherapy. Targeted blockade of the CD73/A2A axis has been shown to impair various aspects of tumorigenesis and displays synergism with other anti-cancer treatments in preclinical studies. Hence, we strongly argue for the development of CD73 inhibitors and for the repositioning of A2A antagonists in cancer.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Faculté de Pharmacie et Institut du Cancer de Montréal , 900 Rue Saint Denis, 10ième étage, Montréal H2X0X9, QC , Canada +514 890 8000 ext: 25170 ; +514 412 7661 ; john.stagg@umontreal.ca.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Allard
authors.forename: Martin
authors.initials: M
authors.lastname: Turcotte
authors.forename: John
authors.initials: J
authors.lastname: Stagg
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015195:Drug Design; D005260:Female; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D000970:Antineoplastic Agents; D058851:GPI-Linked Proteins; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D015720:5'-Nucleotidase; C548241:NT5E protein, human
keywords: CD73; adenosine receptors; immunosuppression; triple negative breast cancer