Targeting the relaxin hormonal pathway in prostate cancer

Abstract

Targeting the androgen signalling pathway has long been the hallmark of anti-hormonal therapy for prostate cancer. However, development of androgen-independent prostate cancer is an inevitable outcome to therapies targeting this pathway, in part, owing to the shift from cancer dependence on androgen signalling for growth in favor of augmentation of other cellular pathways that provide proliferation-, survival-and angiogenesis-promoting signals. This review focuses on the role of the hormone relaxin in the development and progression of prostate cancer, prior to and after the onset of androgen independence, as well as its role in cancers of other reproductive tissues. As the body of literature expands, examining relaxin expression in cancerous tissues and its role in a growing number of in vitro and in vivo cancer models, our understanding of the important involvement of this hormone in cancer biology is becoming clearer. Specifically, the pleiotropic functions of relaxin affecting cell growth, angiogenesis, blood flow, cell migration and extracellular matrix remodeling are examined in the context of cancer progression. The interactions and intercepts of the intracellular signalling pathways of relaxin with the androgen pathway are explored in the context of progression of castration-resistant and androgen-independent prostate cancers. We provide an overview of current anti-hormonal therapeutic treatment options for prostate cancer and delve into therapeutic approaches and development of agents aimed at specifically antagonizing relaxin signalling to curb tumor growth. We also discuss the rationale and challenges utilizing such agents as novel anti-hormonals in the clinic, and their potential to supplement current therapeutic modalities.Steroidal sex hormones-estrogens, androgens and progestogens-have all been implicated in the progression of cancers of different hormone-sensitive tissues.

Cardioprotective actions of relaxin

“…Exogenous Wnt3a is routinely added to stimulate the Here, we tested the hypothesis that the effects of RLX on Nav1.5 and fibrosis are mediated by canonical Wnt signaling. While RLX and Wnt signaling have been investigated in models of cancer[184][185][186], there is no work on the interactions of the RLX and Wnt pathways in adult heart and 'healthy' aging as a precursor of cardiac diseases. We focused on hearts from 9-month (adult) and 24-month-old (aged) Fischer 344/Brown Norway F1 (F-344) male rats obtained from the National Institute of Aging.…”

Genome-wide discovery of hidden genes mediating known drug-disease association using KDDANet

“…All three known target genes, KCNH2, ADRB1 and ADRB2, were included in this subnetwork. Meanwhile, this subnetwork also captured 12 disease- Relaxin signaling pathway, AGE-RAGE signaling pathway and prostate cancer have also been widely investigated and reported in the previous works (Bao, et al, 2015;Neschadim, et al, 2015;Ozvegy-Laczka, et al, 2005). Moreover, autophagy and focal adhesion were two widely observed biological processes in cancer (Eke and Cordes, 2015;Farrow, et al, 2014).…”

COL6A2/3 can serve as potential therapeutic targets and prognostic biomarkers for clear cell renal cell carcinoma

“…Several proteoglycans have been proven to promote tumor progression and metastasis in ccRCC [32,33] . Previous reports have indicated that relaxin could affect cell growth, cell migration, angiogenesis and extracellular matrix remodeling, targeting Relaxin signaling pathway has gradually become a promising therapeutic way in cancer treatment [34,35] . Axon guidance is integral to several basic cellular processes, including organogenesis, regeneration, wound healing.…”