Corrigendum: Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction

Acharya, Munjal M.; Baulch, Janet E.; Lusardi, Theresa A.; Allen, Barrett D.; Chmielewski, Nicole N.; Baddour, Al Anoud D.; Limoli, Charles L.; Boison, Detlev

doi:10.3389/fnmol.2017.00218

Cited by 1 publication

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“…Under basal conditions availability of adenosine is tightly regulated by ADK [236]. While dynamic regulation of ADK gene expression is important to early postnatal brain development, loss or inhibition of ADK promotes pathologies in the brain, e.g., cancer and epilepsy [236,237,238,239,240]. It has been demonstrated that expression changes of ADK in response to brain injury and chemotherapy-induced neuropathic pain impact the levels of protective adenosine and thus disease severity [240,241,242].…”

Section: Impact Of the Adenosinergic Signaling Pathway In Radiatiomentioning

confidence: 99%

“…Adenosine is an endogenous neuroprotectant and modulator of cognition, and dysregulation of adenosine has been linked to radiation-induced cognitive dysfunction [238,239]. Astrocytes control the availability of adenosine though ADK-dependent metabolic clearance.…”

Section: Impact Of the Adenosinergic Signaling Pathway In Radiatiomentioning

confidence: 99%

“…Immunohistochemical analyses in rats demonstrated that exposure to cranial irradiation with 10 Gy triggered activation of ADK in the hippocampus and this was associated with astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Treatment with a pharmacologic inhibitor of ADK for 6 days prior to cranial irradiation significantly improved behavioral performance of the animals at 1 month post exposure and this was associated with reduced levels of radiation-induced astrogliosis and ADK immunoreactivity in the hippocampus [238,239]. The authors concluded that extracellular adenosine exerts neuroprotection against radiation-induced pathology and other neurological comorbidities [239,261].…”

Section: Impact Of the Adenosinergic Signaling Pathway In Radiatiomentioning

confidence: 99%

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The CD73/Ado System—A New Player in RT Induced Adverse Late Effects

Leve

Wirsdörfer

Jendrossek

2019

Cancers

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Radiotherapy (RT) is a central component of standard treatment for many cancer patients. RT alone or in multimodal treatment strategies has a documented contribution to enhanced local control and overall survival of cancer patients, and cancer cure. Clinical RT aims at maximizing tumor control, while minimizing the risk for RT-induced adverse late effects. However, acute and late toxicities of IR in normal tissues are still important biological barriers to successful RT: While curative RT may not be tolerable, sub-optimal tolerable RT doses will lead to fatal outcomes by local recurrence or metastatic disease, even when accepting adverse normal tissue effects that decrease the quality of life of irradiated cancer patients. Technical improvements in treatment planning and the increasing use of particle therapy have allowed for a more accurate delivery of IR to the tumor volume and have thereby helped to improve the safety profile of RT for many solid tumors. With these technical and physical strategies reaching their natural limits, current research for improving the therapeutic gain of RT focuses on innovative biological concepts that either selectively limit the adverse effects of RT in normal tissues without protecting the tumor or specifically increase the radiosensitivity of the tumor tissue without enhancing the risk of normal tissue complications. The biology-based optimization of RT requires the identification of biological factors that are linked to differential radiosensitivity of normal or tumor tissues, and are amenable to therapeutic targeting. Extracellular adenosine is an endogenous mediator critical to the maintenance of homeostasis in various tissues. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5′ ectonucleotidase (NT5E, CD73) that catabolize ATP to adenosine. Recent work revealed a role of the immunoregulatory CD73/adenosine system in radiation-induced fibrotic disease in normal tissues suggesting a potential use as novel therapeutic target for normal tissue protection. The present review summarizes relevant findings on the pathologic roles of CD73 and adenosine in radiation-induced fibrosis in different organs (lung, skin, gut, and kidney) that have been obtained in preclinical models and proposes a refined model of radiation-induced normal tissue toxicity including the disease-promoting effects of radiation-induced activation of CD73/adenosine signaling in the irradiated tissue environment. However, expression and activity of the CD73/adenosine system in the tumor environment has also been linked to increased tumor growth and tumor immune escape, at least in preclinical models. Therefore, we will discuss the use of pharmacologic inhibition of CD73/adenosine-signaling as a promising strategy for improving the therapeutic gain of RT by targeting both, malignant tumor growth and adverse late effects of RT with a focus on fibrotic disease. The consideration of the the...

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Section: Impact Of the Adenosinergic Signaling Pathway In Radiatiomentioning

confidence: 99%

Section: Impact Of the Adenosinergic Signaling Pathway In Radiatiomentioning

confidence: 99%

Section: Impact Of the Adenosinergic Signaling Pathway In Radiatiomentioning

confidence: 99%

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The CD73/Ado System—A New Player in RT Induced Adverse Late Effects

Leve

Wirsdörfer

Jendrossek

2019

Cancers

View full text Add to dashboard Cite

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Corrigendum: Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction

Cited by 1 publication

References 0 publications

The CD73/Ado System—A New Player in RT Induced Adverse Late Effects

The CD73/Ado System—A New Player in RT Induced Adverse Late Effects

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