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胰腺腺癌中的G蛋白偶联受体:肿瘤生物学的促成因素及新型治疗靶点

GPCRs in pancreatic adenocarcinoma: Contributors to tumour biology and novel therapeutic targets.

作者信息

Sriram Krishna, Salmerón Cristina, Wiley Shu Z, Insel Paul A

机构信息

Department of Pharmacology, University of California San Diego, La Jolla, California.

Department of Medicine, University of California San Diego, La Jolla, California.

出版信息

Br J Pharmacol. 2020 Jun;177(11):2434-2455. doi: 10.1111/bph.15028. Epub 2020 Apr 12.

Abstract

Pancreatic cancer has one of the highest mortality rates (5-year survival ~9%) among cancers. Pancreatic adenocarcinoma (PAAD) is the most common (>80%) and the most lethal type of pancreatic cancer. A need exists for new approaches to treat pancreatic adenocarcinoma. GPCRs, the largest family of cell-surface receptors and drug targets, account for ~35% of approved drugs. Recent studies have revealed roles for GPCRs in PAAD cells and cells in the tumour micro-environment. This review assesses current information regarding GPCRs in PAAD by summarizing omics data for GPCRs expression in PAAD. The PAAD "GPCRome" includes GPCRs with approved agents, thereby offering potential for their repurposing/repositioning. We then reviewed the evidence for functional roles of specific GPCRs in PAAD. We also highlight gaps in understanding the contribution of GPCRs to PAAD biology and identify several GPCRs that may be novel therapeutic targets for future work in search of GPCR-targeted drugs to treat PAAD tumours.

摘要

胰腺癌是癌症中死亡率最高的疾病之一(5年生存率约为9%)。胰腺腺癌(PAAD)是最常见(>80%)且最致命的胰腺癌类型。因此,需要新的方法来治疗胰腺腺癌。G蛋白偶联受体(GPCRs)是细胞表面受体和药物靶点中最大的家族,约占已批准药物的35%。最近的研究揭示了GPCRs在PAAD细胞和肿瘤微环境中的细胞中的作用。本综述通过总结PAAD中GPCRs表达的组学数据,评估了有关PAAD中GPCRs的当前信息。PAAD的“GPCRome”包括具有已批准药物的GPCRs,因此为其重新利用/重新定位提供了潜力。然后,我们回顾了特定GPCRs在PAAD中功能作用的证据。我们还强调了在理解GPCRs对PAAD生物学贡献方面的差距,并确定了几种GPCRs,它们可能是未来寻找治疗PAAD肿瘤的GPCR靶向药物工作中的新型治疗靶点。

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