Targeting cancer-derived adenosine: new therapeutic approaches.
Identifieur interne : 000638 ( PubMed/Checkpoint ); précédent : 000637; suivant : 000639Targeting cancer-derived adenosine: new therapeutic approaches.
Auteurs : Arabella Young ; Deepak Mittal ; John Stagg [Canada] ; Mark J. Smyth [Australie]Source :
- Cancer discovery [ 2159-8290 ] ; 2014.
English descriptors
- KwdEn :
- 5'-Nucleotidase (antagonists & inhibitors), 5'-Nucleotidase (immunology), Adenosine (immunology), Adenosine (metabolism), Animals, Antigens, CD (immunology), Apyrase (antagonists & inhibitors), Apyrase (immunology), GPI-Linked Proteins (antagonists & inhibitors), GPI-Linked Proteins (immunology), Humans, Immunosuppressive Agents (therapeutic use), Mice, Molecular Targeted Therapy, Neoplasms (drug therapy), Neoplasms (immunology), Neoplasms (pathology), Purinergic P1 Receptor Antagonists.
- MESH :
- chemical , antagonists & inhibitors : 5'-Nucleotidase, Apyrase, GPI-Linked Proteins.
- chemical , immunology : 5'-Nucleotidase, Adenosine, Antigens, CD, Apyrase, GPI-Linked Proteins.
- chemical , metabolism : Adenosine.
- chemical , therapeutic use : Immunosuppressive Agents.
- drug therapy : Neoplasms.
- immunology : Neoplasms.
- pathology : Neoplasms.
- Animals, Humans, Mice, Molecular Targeted Therapy, Purinergic P1 Receptor Antagonists.
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.
DOI: 10.1158/2159-8290.CD-14-0341
PubMed: 25035124
Affiliations:
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pubmed:25035124Le document en format XML
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<front><div type="abstract" xml:lang="en">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.</div>
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<Abstract><AbstractText Label="UNLABELLED">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.</AbstractText>
<AbstractText Label="SIGNIFICANCE" NlmCategory="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.</AbstractText>
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