Sex hormone receptor signaling in bladder cancer: A potential target for enhancing the efficacy of conventional non‐surgical therapy

Abstract

There have been critical problems in the non‐surgical treatment for bladder cancer, espe-cially residence to intravesical pharmacotherapy, including BCG immunotherapy, cisplatin‐based chemotherapy, and radiotherapy. Recent preclinical and clinical evidence has suggested a vital role of sex steroid hormone‐mediated signaling in the progression of urothelial cancer. Moreover, activation of the androgen receptor and estrogen receptor pathways has been implicated in modulating sensitivity to conventional non‐surgical therapy for bladder cancer. This may indicate the possibility of anti‐androgenic and anti‐estrogenic drugs, apart from their direct anti‐tumor activity, to function as sensitizers of such conventional treatment. This article summarizes available data suggesting the involvement of sex hormone receptors, such as androgen receptor, estrogen receptor‐α, and estrogen receptor‐β, in the progression of urothelial cancer, focusing on their modulation for the efficacy of conventional therapy, and discusses their potential of overcoming therapeutic resistance.