Clinical and therapeutic implications of sex steroid hormone receptor status in urothelial bladder cancer

Abstract

Studies on the clinical profile of urothelial bladder cancer (UBC) have shown significant gender differences, namely, higher occurrence in males (male-to-female ratio of 3.5:1) and an advanced stage of disease at the time of diagnosis with rapid progression of the disease after initial diagnosis seen more commonly in females. The relationship between gender and UBC is complex and probably influenced by biological and epidemiological factors. Potential contributory factors such as sex steroid hormone pathway, gender difference in environmental carcinogen exposure, metabolic enzyme activity, and disparities in the intensity of diagnostic evaluation could probably explain the demographic trends in UBC. This comprehensive review of Medline publications during the period 2009–2019 attempts to identify the possible role of sex hormone receptors in gender variation and sexual dimorphism in the occurrence and progression of UBC. The clinical implications of identifying sex steroid receptors on factors such as disease prognostication and the therapeutic role of anti-androgens in the prevention and progression of UBC are critically reviewed. There is now significant evidence in literature to suggest the possible role of sex steroid hormone receptor-mediated signals in the genesis and progression of UBC. These receptors include androgen receptors, estrogen receptors, progesterone receptors, and various other orphan receptors. Excessive or reduced expression of these receptors, as well as alterations in their upstream or downstream pathways, correlate well with the clinical and therapeutic outcomes of UBC.

Inhibition of Androgen Signalling Improves the Outcomes of Therapies for Bladder Cancer: Results from a Systematic Review of Preclinical and Clinical Evidence and Meta-Analysis of Clinical Studies

“…Therefore, new treatment strategies have been advocated to improve the outcomes of treatments for BCa [ 3 ]. The evidence demonstrates significant gender-related differences in patients with BCa in terms of both incidence and natural history [ 5 ]. Indeed, incidence is higher in males with a male-to-female ratio of 3.5:1, while advanced stage at the time of diagnosis and rapid progression are commonly observed in females [ 5 ].…”

“…The evidence demonstrates significant gender-related differences in patients with BCa in terms of both incidence and natural history [ 5 ]. Indeed, incidence is higher in males with a male-to-female ratio of 3.5:1, while advanced stage at the time of diagnosis and rapid progression are commonly observed in females [ 5 ]. The role of androgen signalling in BCa has been proven in preclinical and clinical settings and these findings have potential relevant therapeutic implications [ 6 , 7 ].…”

Impact of Androgen Suppression Therapy on the Risk and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis

“…Sex hormones and corresponding receptors are relevant modulators of cancer onset and progression in nonreproductive organs, particularly the lung, colorectal, bladder, stomach, kidney, pancreas, and thyroid gland ( 8 ). The excessive or reduced expression of these receptors, and the changes in their upstream or downstream pathways are closely related to the outcomes of BCa ( 8 , 9 ). Numerous studies have focused on the role of androgen receptor (AR) and androgens in the development of bladder cancer.…”

Bisphenol A Alters the Energy Metabolism of Stromal Cells and Could Promote Bladder Cancer Progression

“…Growing evidence has shown the pro-tumorigenic effect of BPA [4][5][6] in many cancers, especially hormone-dependent cancers such as breast [5] and prostate cancer [7]. Although bladder tissue is not recognized as a hormone-sensitive tissue, studies have demonstrated the role of hormone receptors in bladder cancer initiation and progression [8,9], as well as their impact on treatment [20] and prognosis [21]. As the impact of BPA on bladder cancer has not yet been reported, the effects of BPA on the stromal environment of bladder cancer were studied through bladder fibroblasts and CAFs.…”