Purinergic signalling pathway: therapeutic target in ovarian cancer

Abstract

Abstract Background The lack of early diagnostic tools and the development of chemoresistance have made ovarian cancer (OC) one of the deadliest gynaecological cancers. The tumour microenvironment is characterised by the extracellular release of high levels of ATP, which is followed by the activation of P1 adenosinergic and P2 purinergic signalling systems. The sequential hydrolysis of ATP by the ectonucleotidases CD39 and CD73 generates adenosine, which creates an immune suppressive microenvironment by inhibiting the T and NK cell responses via the A2A adenosine receptor. Main body of the abstract In OC, adenosine-induced pAMPK pathway leads to the inhibition of cell growth and proliferation, which offers new treatment options to prevent or overcome chemoresistance. The activation of P2Y12 and P2Y1 purinergic receptors expressed in the platelets promotes epithelial-mesenchymal transition (EMT). The inhibitors of these receptors will be the effective therapeutic targets in managing OC. Furthermore, research on these signalling systems indicates an expanding field of opportunities to specifically target the purinergic receptors for the treatment of OC. Short conclusion In this review, we have described the complex purinergic signalling mechanism involved in the development of OC and discussed the merits of targeting the components involved in the purinergic signalling pathway.

Keywords

• Adenosine
• Ectonucleotidases
• Chemoresistance
• Platelets
• Purinergic signalling
• Ovarian cancer (OC)