Shah Himani, Fairlie David P, Lim Junxian
Centre for Chemistry and Drug Discovery and ARC Centre of Excellence for Innovations in Peptide and Protein Science, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Centre for Chemistry and Drug Discovery and ARC Centre of Excellence for Innovations in Peptide and Protein Science, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
J Pharmacol Exp Ther. 2025 Jan;392(1):100016. doi: 10.1124/jpet.124.002176. Epub 2024 Nov 22.
Cancers affecting women, such as breast, uterine, ovarian, endometrial, and cervical cancers, have become increasingly prevalent. The growing incidence and death rates associated with these cancers warrant the development of innovative and alternative approaches to current treatments. This article investigates the association of women's cancers with a molecular target known as protease-activated receptor 2 (PAR2), a G protein-coupled receptor that is expressed on the surface of cancer cells. Expression levels of the PAR2 gene were curated from publicly available databases, and PAR2 was found to be significantly overexpressed in tissues from patients with breast, uterine, ovarian, endometrial, or cervical cancer compared with normal tissues. PAR2 overexpression has been previously linked to tumor progression and, in some cases, tumor growth. Activation of PAR2 by either endogenous proteases or synthetic agonists triggers certain downstream intracellular signaling pathways that have been associated with tumor progression, cell migration and invasion, angiogenesis, and apoptosis of cancer cells. Although recent advances have led to identification of several PAR2 antagonists, none has yet been developed for human use. Additionally, PAR2 inhibition has been shown to increase the efficacy of chemotherapeutic drugs, allowing them to be potentially used at less toxic doses in combination therapies for cancer. The present work briefly summarizes the current status of PAR2 as a potential therapeutic target for treating women's cancers. SIGNIFICANCE STATEMENT: This article highlights potential roles for protease-activated receptor 2 (PAR2) in cancers affecting women. Overexpression of the PAR2 gene in women's cancers is associated with various oncogenic processes, such as tumor progression, cell migration, and invasion, ultimately contributing to poorer patient prognoses. Given the increasing incidence of women's cancers, there is an urgent need to develop novel therapeutic drugs, and PAR2 represents a promising target for developing new treatments.
影响女性的癌症，如乳腺癌、子宫癌、卵巢癌、子宫内膜癌和宫颈癌，已变得越来越普遍。与这些癌症相关的发病率和死亡率不断上升，这就需要开发创新的和替代现有治疗方法的途径。本文研究了女性癌症与一种名为蛋白酶激活受体2（PAR2）的分子靶点之间的关联，PAR2是一种G蛋白偶联受体，在癌细胞表面表达。PAR2基因的表达水平来自公开可用的数据库，结果发现与正常组织相比，PAR2在乳腺癌、子宫癌、卵巢癌、子宫内膜癌或宫颈癌患者的组织中显著过表达。PAR2过表达先前已与肿瘤进展相关，在某些情况下还与肿瘤生长相关。内源性蛋白酶或合成激动剂激活PAR2会触发某些下游细胞内信号通路，这些通路与肿瘤进展、细胞迁移和侵袭、血管生成以及癌细胞凋亡有关。尽管最近的进展已导致鉴定出几种PAR2拮抗剂，但尚未有用于人类的产品开发出来。此外，已证明抑制PAR2可提高化疗药物的疗效，使其有可能在联合癌症治疗中以较低毒性剂量使用。本研究简要总结了PAR2作为治疗女性癌症潜在治疗靶点的现状。意义声明：本文强调了蛋白酶激活受体2（PAR2）在影响女性的癌症中的潜在作用。PAR2基因在女性癌症中的过表达与各种致癌过程相关，如肿瘤进展、细胞迁移和侵袭，最终导致患者预后较差。鉴于女性癌症发病率不断上升，迫切需要开发新型治疗药物，而PAR2是开发新疗法的一个有希望的靶点。
