Table 2.

Treatment possibilities for BC targeting the purinergic system, and its clinical outcomes

Treatment possibility	Analysis phase	Effects on BC control	References
Ivermectin	Preclinical studies with the human MDA-MB-231, MCF-7, and SKBR3 lineages, and in 4T1.2 Balb/c triple negative mice breast cancer cells	Promotes cell death in mice and humans lineages through P2X4/P2X7/Pannexin-1 associated with caspases 1 and 3	[209]
Ticagrelor	Preclinical studies with the MDA-MB-468, MDA-MB-231, and MCF-7 lineages	Promotes P2Y12 blockade, decreased the interaction between human breast tumor cells and platelets, decreasing the metastatic process	[120]
Non-selective AR antagonists - aminophylline (AMO) - and selective A2B antagonists (ATL801)	Preclinical studies with metastatic cells 4T1.12B - studies in Balb/c mice.	Growth retardation of 4T1.12B breast cancer cells and their lung metastasis, by blocking AR	[210]
A2A antagonist (CPI-444) with anti-PD1 mAb	Preclinical studies with metastatic 4T1.2 cells in Balb/c and C57BL/6 mice	TNBC metastasis reduction	[173]
Monoclonal antibody IE9 and 7G2	In vitro T lymphocytes treatment	Inhibition of cell-bound CD73 enzymatic activity. IE9 is able to induce lymphocyte proliferation when combined with other drugs	[211]
Monoclonal antibody 4G4	Preclinical studies in mice	Performs an inhibition of platelet aggregation onto endothelial cells and a weaker inhibition of CD73	[212]
Monoclonal antibody AD2	Preclinical studies with MDA-MB-231 lineage	Promotes an internalization of CD73, reducing its activity.	[176]
Monoclonal antibody 3F7	Preclinical studies with human MDA-MB-231 and MDA-MB-468, and in mouse 4T1 cell lines	Endothelial cells migration inhibition, and is able to bind to CD73, decreasing its activity	[213]
Suppression of CD73 by shRNA	Preclinical studies with MDA-MB-231 and MCF-7 cell lines	By suppressing CD73, it prevents the proliferation of MDA-MB-231 cells, inducing apoptosis and arrest of the cell cycle	[177]
Specific inhibitor of CD73 activity (APCP)	Preclinical studies with MDA-MB-231 and MCF-7 cell lines	By suppressing CD73, it prevents the proliferation of MDA-MB-231 cells	[177]