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Sorrentino et al. J Cancer Metastasis Treat 2017;3:127-38 Journal of
DOI: 10.20517/2394-4722.2017.29
Cancer Metastasis and Treatment

www.jcmtjournal.com
Review Open Access

Role of adenosine in tumor progression:

focus on A receptor as potential
2B
therapeutic target

Claudia Sorrentino , Silvana Morello 1
1,2
1 Department of Pharmacy, University of Salerno, 84084 Fisciano (SA), Italy.
2 PhD Program in Drug Discovery and Development, Department of Pharmacy, University of Salerno, 84084 Fisciano (SA), Italy.

Correspondence to: Dr. Silvana Morello, Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
E-mail: smorello@unisa.it
How to cite this article: Sorrentino C, Morello S. Role of adenosine in tumor progression: focus on A receptor as potential therapeutic target. J
2B
Cancer Metastasis Treat 2017;3:127-38.
ABSTRACT

Article history: Adenosine receptors are a family of G-coupled receptors which mediate the anti-
Received: 08-05-2017 inflammatory and immune-suppressive effects of adenosine in a damaged tissue. A large
Accepted: 07-07-2017 number of evidence indicate that the accumulation of adenosine under hypoxic conditions
Published: 17-07-2017 favors tumor progression, helping cancer cells to evade immune responses. Tumor cells and/
or lymphoid and myeloid cells can express the adenosine-generating enzyme CD73 and/or
Key words: A receptor, which in turn strongly suppresses an effective T-cell-mediated response, while
CD73/A adenosine receptors promotes the activity of suppressive cells such as Treg and myeloid-derived suppressor
2A
2
axis, cells. CD73 inhibitors and A antagonists, either as single agents, or in combination with
2A
A adenosine receptor, immune-checkpoints inhibitors such as anti PD-1 monoclonal antibodies, are currently
2B
tumor immunity, in Phase I clinical trial in cancer patients. Recent studies show that A receptor plays an
2B
tumor metastasis, important role in mediating the pro-tumor effects of adenosine, since its selective blockade
tumor angiogenesis, can inhibit tumor growth in some murine tumor models. Targeting A receptor reduces
2B
cancer treatment immunosuppression induced by myeloid cells and inhibits the stromal cells activity within
the tumor microenvironment, limiting tumor angiogenesis and metastatic processes. Here,
the authors review the current data on involvement of A receptor in regulating tumor
2B
progression and discuss the development of A receptor inhibitors as potential therapeutic
2B
agents in cancer treatment.
INTRODUCTION In the eternal battle against cancer, several strategies
have been developed. One of the first approach to treat
Tumor microenvironment is populated not only by cancer has been the antineoplastic chemotherapy which
malignant cells but also by other stromal cells and is made up of chemical substances that provide to halt
immune cells that cooperate to the development of directly the highly-replicating tumor cells by damaging
cancer. [1,2] their RNA or DNA. Radiotherapy is another important
[3]
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