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Purinergic signalling pathway: therapeutic target in ovarian cancer
Egyptian Journal of Medical Human Genetics Pub Date : 2020-06-01 , DOI: 10.1186/s43042-020-00059-3
Nisha Chandran , Mahalaxmi Iyer , Zothan Siama , Balachandar Vellingiri , Arul Narayanasamy

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. 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. 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.

中文翻译:

嘌呤能信号通路:卵巢癌的治疗靶点

早期诊断工具的缺乏和化疗耐药性的发展使卵巢癌 (OC) 成为最致命的妇科癌症之一。肿瘤微环境的特点是细胞外释放高水平的 ATP,随后激活 P1 腺苷能和 P2 嘌呤能信号系统。外核苷酸酶 CD39 和 CD73 对 ATP 的连续水解产生腺苷,腺苷通过 A2A 腺苷受体抑制 T 和 NK 细胞反应来创建免疫抑制微环境。在 OC 中,腺苷诱导的 pAMPK 通路导致细胞生长和增殖的抑制,这为预防或克服化学抗性提供了新的治疗选择。血小板中表达的 P2Y12 和 P2Y1 嘌呤能受体的激活促进上皮间质转化 (EMT)。这些受体的抑制剂将成为控制 OC 的有效治疗靶点。此外,对这些信号系统的研究表明,专门针对嘌呤能受体治疗 OC 的机会不断扩大。在这篇综述中,我们描述了参与 OC 发展的复杂嘌呤能信号机制,并讨论了靶向嘌呤能信号通路中涉及的成分的优点。对这些信号系统的研究表明,专门针对嘌呤能受体治疗 OC 的机会不断扩大。在这篇综述中,我们描述了参与 OC 发展的复杂嘌呤能信号机制,并讨论了靶向嘌呤能信号通路中涉及的成分的优点。对这些信号系统的研究表明,专门针对嘌呤能受体治疗 OC 的机会不断扩大。在这篇综述中,我们描述了参与 OC 发展的复杂嘌呤能信号机制,并讨论了靶向嘌呤能信号通路中涉及的成分的优点。
更新日期:2020-06-01
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