Targeting CD73 and downstream adenosine receptor signaling in triple-negative breast cancer

Expert Opin Ther Targets. 2014 Aug;18(8):863-81. doi: 10.1517/14728222.2014.915315. Epub 2014 May 6.


Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: CD73; adenosine receptors; immunosuppression; triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 5'-Nucleotidase / antagonists & inhibitors
  • 5'-Nucleotidase / metabolism*
  • Adenosine A1 Receptor Antagonists / pharmacology
  • Animals
  • Antineoplastic Agents / pharmacology
  • Drug Design
  • Female
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Receptor, Adenosine A2A / drug effects
  • Receptor, Adenosine A2A / metabolism*
  • Receptor, Adenosine A2B / metabolism
  • Signal Transduction
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology


  • Adenosine A1 Receptor Antagonists
  • Antineoplastic Agents
  • GPI-Linked Proteins
  • Receptor, Adenosine A2A
  • Receptor, Adenosine A2B
  • 5'-Nucleotidase
  • NT5E protein, human