Inhibition of the adenosinergic pathway: the indispensable part of oncological therapy in the future

Huang, Yong; Gu, Zili; Yang, Qifeng; Zhai, Guangxi; Zhao, Xiaogang; Sun, Qing; Shi, Yanbin; Lin, Guimei

doi:10.1007/s11302-018-9641-4

Cited by 13 publications

(12 citation statements)

References 182 publications

(222 reference statements)

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“…Also, the A2B receptor is related to increased resistance to doxorubicin in the treatment of BC (Table 1 ) [ 108 ]. Therefore, its inhibition decreases the growth and metastatic potential of ER negative breast tumors and TNBC, in addition to promoting a better response to chemotherapy treatment [ 101 , 122 , 123 ].…”

Section: Main Purinergic Receptorsmentioning

confidence: 99%

“…It is known that CD73 is related to a worse prognosis in TNBC and HER2 positive BC [ 123 ]; therefore, studies in mice found that silencing the CD73 gene in BC cells led to a decrease in levels of focal adhesion kinase (FAK), which is related to cells adhesion and migration. The use of anti-CD73 mAb slows the growth of cancer cells and TNBC metastasis [ 102 , 221 ] to the lung [ 218 ], in addition to reducing tumor angiogenesis in mouse models with BC [ 219 ].…”

Section: Therapeutic Optionsmentioning

confidence: 99%

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Targeting the purinergic pathway in breast cancer and its therapeutic applications

Araújo

Kerkhoff

Maciel

et al. 2021

Purinergic Signalling

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Breast cancer (BC) is the most frequent cause of death among women, representing a global public health problem. Here, we aimed to discuss the correlation between the purinergic system and BC, recognizing therapeutic targets. For this, we analyzed the interaction of extracellular nucleotides and nucleosides with the purinergic receptors P1 and P2, as well as the influence of ectonucleotidase enzymes (CD39 and CD73) on tumor progression. A comprehensive bibliographic search was carried out. The relevant articles for this review were found in the PubMed, Scielo, Lilacs, and ScienceDirect databases. It was observed that among the P1 receptors, the A1, A2A, and A2B receptors are involved in the proliferation and invasion of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets.

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Section: Main Purinergic Receptorsmentioning

confidence: 99%

Section: Therapeutic Optionsmentioning

confidence: 99%

Targeting the purinergic pathway in breast cancer and its therapeutic applications

Araújo

Kerkhoff

Maciel

et al. 2021

Purinergic Signalling

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“…In the last 10 years, cancer research has especially focused on the role played by Ado-, CD39-, and CD73-producing ectoenzymes in immunomodulation and evasion of the antitumor immune response. In fact, inhibition of the adenosinergic pathway in the tumor microenvironment has been proposed as an indispensable alternative in oncological therapy [ 36 , 37 ]. However, large gaps in knowledge prevent the development of effective Ado-based therapies, such as the roles of redundant pathways that control ATP and Ado levels.…”

Section: Discussionmentioning

confidence: 99%

Detection of CD39 and a Highly Glycosylated Isoform of Soluble CD73 in the Plasma of Patients with Cervical Cancer: Correlation with Disease Progression

Muñóz-Godínez

Mora‐García²,

Weiss‐Steider³

et al. 2020

Mediators of Inflammation

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Persistent infection with high-risk human papillomavirus (HR-HPV) is the main factor in the development of cervical cancer (CC). The presence of immunosuppressive factors plays an important role in the development of this type of cancer. To determine whether CD39 and CD73, which participate in the production of immunosuppressive adenosine (Ado), are involved in the progression of CC, we compared the concentrations and hydrolytic activity of these ectonucleotidases in platelet-free plasma (PFP) samples between patients with low-grade squamous intraepithelial lesions (LSILs) ( n = 18 ), high-grade squamous intraepithelial lesions (HSILs) ( n = 12 ), and CC ( n = 19 ) and normal donors (NDs) ( n = 15 ). The concentrations of CD39 and CD73 in PFP increased with disease progression ( r = 0.5929 , p < 0.001 ). The PFP of patients with HSILs or CC showed the highest concentrations of CD39 (2.3 and 2.2 times that of the NDs, respectively) and CD73 (1.7 and 2.68 times that of the NDs, respectively), which were associated with a high capacity to generate Ado from the hydrolysis of adenosine diphosphate (ADP) and adenosine monophosphate (AMP). The addition of POM-1 and APCP, specific inhibitors of CD39 and CD73, respectively, inhibited the ADPase and AMPase activity of PFP by more than 90%. A high level of the 90 kD isoform of CD73 was detected in the PFP of patients with HSILs or CC. Digestion with endoglycosidase H and N-glycanase generated CD73 with weights of approximately 90 kD, 85 kD, 80 kD, and 70 kD. In addition, the levels of transforming grow factor-β (TGF-β) in the PFPs of patients with LSIL, HSIL and CC positively correlated with those of CD39 ( r = 0.4432 , p < 0.001 ) and CD73 ( r = 0.5786 , p < 0.001 ). These results suggest that persistent infection by HR-HPV and the concomitant production of TGF-β promote the expression of CD39 and CD73 to favor CC progression through Ado generation.

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“…Conversely, increased adenosine metabolism is now recognized as a characteristic of many types of cancer. Elevated adenosine, and its metabolic precursor adenosine triphosphate (ATP), promote cancer growth and play a role in host immunosuppression in the tumor microenvironment (TME) [ 36 , 40 , 41 , 42 , 43 ].…”

Section: Cancer Incidence In Schizophreniamentioning

confidence: 99%

Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?

Hamoud

Bach

Kakrecha

et al. 2022

IJMS

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For over a century, a complex relationship between schizophrenia diagnosis and development of many cancers has been observed. Findings from epidemiological studies are mixed, with reports of increased, reduced, or no difference in cancer incidence in schizophrenia patients. However, as risk factors for cancer, including elevated smoking rates and substance abuse, are commonly associated with this patient population, it is surprising that cancer incidence is not higher. Various factors may account for the proposed reduction in cancer incidence rates including pathophysiological changes associated with disease. Perturbations of the adenosine system are hypothesized to contribute to the neurobiology of schizophrenia. Conversely, hyperfunction of the adenosine system is found in the tumor microenvironment in cancer and targeting the adenosine system therapeutically is a promising area of research in this disease. We outline the current biochemical and pharmacological evidence for hypofunction of the adenosine system in schizophrenia, and the role of increased adenosine metabolism in the tumor microenvironment. In the context of the relatively limited literature on this patient population, we discuss whether hypofunction of this system in schizophrenia, may counteract the immunosuppressive role of adenosine in the tumor microenvironment. We also highlight the importance of studies examining the adenosine system in this subset of patients for the potential insight they may offer into these complex disorders.

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Inhibition of the adenosinergic pathway: the indispensable part of oncological therapy in the future

Cited by 13 publications

References 182 publications

Targeting the purinergic pathway in breast cancer and its therapeutic applications

Targeting the purinergic pathway in breast cancer and its therapeutic applications

Detection of CD39 and a Highly Glycosylated Isoform of Soluble CD73 in the Plasma of Patients with Cervical Cancer: Correlation with Disease Progression

Adenosine, Schizophrenia and Cancer: Does the Purinergic System Offer a Pathway to Treatment?

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