Administration of P2X7 Receptor Blockers in Oncological Experimental Models

Marchi, Elena De; Pegoraro, Anna; Adinolfi, Elena

doi:10.1007/978-1-0716-2384-8_17

Cited by 2 publications

(3 citation statements)

References 32 publications

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“…As the above-cited literature demonstrate, P2X7 growth-promoting roles have been covered elsewhere; therefore, its extensive characterization is beyond the scope of the present overview. The wealth of observations on P2X7 in such a plethora of cancers suggest that the receptor acts as a positive regulator of tumor formation and evolution and, therefore, that its pharmacological blockade could be advantageous for oncological patients [ 14 , 78 ]. However, in the TME, P2X7 is expressed not only by cancer cells but also by many components of the innate and cell-mediated immunity, and it plays a role in both pro-inflammatory and tolerogenic responses [ 12 , 13 ].…”

Section: The P2x7 Receptor In Cancer Growth and Immune Responsesmentioning

confidence: 99%

“…Given the involvement of the P2X7 receptor in the aforementioned metastasis-promoting signaling pathways and mechanisms, it is not surprising that overexpression of the receptor was associated with metastatic stages of multiple cancers [ 43 , 55 , 101 , 114 , 115 , 116 , 117 , 118 ]. Accordingly, P2X7 antagonism proved efficacious in reducing the in vivo dissemination of cancer cells in animal models of metastasis [ 41 , 43 , 78 , 91 , 92 , 96 , 119 ].…”

Section: P2x7 and Metastasismentioning

confidence: 99%

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The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

Adinolfi,

De Marchi,

Grignolo

et al. 2023

IJMS

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The tumor niche is an environment rich in extracellular ATP (eATP) where purinergic receptors have essential roles in different cell subtypes, including cancer, immune, and stromal cells. Here, we give an overview of recent discoveries regarding the role of probably the best-characterized purinergic receptor in the tumor microenvironment: P2X7. We cover the activities of the P2X7 receptor and its human splice variants in solid and liquid cancer proliferation, dissemination, and crosstalk with immune and endothelial cells. Particular attention is paid to the P2X7-dependent release of microvesicles and exosomes, their content, including ATP and miRNAs, and, in general, P2X7-activated mechanisms favoring metastatic spread and niche conditioning. Moreover, the emerging role of P2X7 in influencing the adenosinergic axis, formed by the ectonucleotidases CD39 and CD73 and the adenosine receptor A2A in cancer, is analyzed. Finally, we cover how antitumor therapy responses can be influenced by or can change P2X7 expression and function. This converging evidence suggests that P2X7 is an attractive therapeutic target for oncological conditions.

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Section: The P2x7 Receptor In Cancer Growth and Immune Responsesmentioning

confidence: 99%

Section: P2x7 and Metastasismentioning

confidence: 99%

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

Adinolfi,

De Marchi,

Grignolo

et al. 2023

IJMS

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“…Indeed, P2X7 is associated with the development and progression of diverse diseases, including brain disorders [ 18 , 19 ], autoimmune diseases [ 20 , 21 ], blood malignancies [ 22 ], and cancer. [ 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

P2X7 Variants in Pathophysiology

Pegoraro,

Grignolo,

Ruo

et al. 2024

IJMS

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P2X7 receptor activation by extracellular adenosine triphosphate (eATP) modulates different intracellular pathways, including pro-inflammatory and tumor-promoting cascades. ATP is released by cells and necrotic tissues during stressful conditions and accumulates mainly in the inflammatory and tumoral microenvironments. As a consequence, both the P2X7 blockade and agonism have been proposed as therapeutic strategies in phlogosis and cancer. Nevertheless, most studies have been carried out on the WT fully functional receptor variant. In recent years, the discovery of P2X7 variants derived by alternative splicing mechanisms or single-nucleotide substitutions gave rise to the investigation of these new P2X7 variants’ roles in different processes and diseases. Here, we provide an overview of the literature covering the function of human P2X7 splice variants and polymorphisms in diverse pathophysiological contexts, paying particular attention to their role in oncological and neuroinflammatory conditions.

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Administration of P2X7 Receptor Blockers in Oncological Experimental Models

Cited by 2 publications

References 32 publications

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

P2X7 Variants in Pathophysiology

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