Extracellular ATP and Adenosine in Cancer Pathogenesis and Treatment

Anna M Chiarella; Yun K Ryu; Gulam A Manji; Anil K Rustgi

doi:10.1016/j.trecan.2021.04.008

Extracellular ATP and Adenosine in Cancer Pathogenesis and Treatment

Trends Cancer. 2021 Aug;7(8):731-750. doi: 10.1016/j.trecan.2021.04.008. Epub 2021 May 29.

Authors

Anna M Chiarella¹, Yun K Ryu², Gulam A Manji³, Anil K Rustgi⁴

Affiliations

¹ Herbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: ac4577@cumc.columbia.edu.
² Herbert Irving Comprehensive Cancer Center, Division of Hematology-Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
³ Herbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Division of Hematology-Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
⁴ Herbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.

PMID: 34074623
DOI: 10.1016/j.trecan.2021.04.008

Abstract

ATP hydrolysis and downstream signaling pathways in the extracellular space have a major impact upon tumor progression and metastasis. The complexity and interdependence of various cell types in the extracellular space have been increasingly appreciated in recent years. With increased awareness of the importance of this signaling pathway in the pathogenic development and progression of malignancies, there has been attention to therapeutic strategies targeting extracellular adenosine metabolism and signaling. This review summarizes the molecular and physiologic roles of extracellular ATP and adenosine in normal and disease states, and potential therapeutic applications.

Keywords: CD39; CD73; cancer; extracellular ATP; extracellular adenosine; purinergic signaling.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Adenosine / metabolism*
Adenosine Triphosphate / metabolism*
Animals
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Cell Line, Tumor
Clinical Trials as Topic
Disease Models, Animal
Drug Resistance, Neoplasm / drug effects
Drug Resistance, Neoplasm / immunology
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Neoplasms / drug therapy*
Neoplasms / immunology
Neoplasms / metabolism
Neoplasms / pathology
Progression-Free Survival
Purinergic P1 Receptor Antagonists / pharmacology
Purinergic P1 Receptor Antagonists / therapeutic use
Purinergic P2 Receptor Antagonists / pharmacology
Purinergic P2 Receptor Antagonists / therapeutic use
Receptors, Purinergic P1 / metabolism
Receptors, Purinergic P2 / metabolism
Signal Transduction / drug effects
Signal Transduction / immunology
Xenograft Model Antitumor Assays

Substances

Immune Checkpoint Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic P2 Receptor Antagonists
Receptors, Purinergic P1
Receptors, Purinergic P2
Adenosine Triphosphate
Adenosine