Protease-activated receptor 2: A promising therapeutic target for women's cancers

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. (c) 2024 Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics.