Pharmacotherapy of urethral stricture

Abstract

Urethral stricture is characterized by the chronic formation of fibrous tissue, leading to the narrowing of the urethral lumen. Despite the availability of various endoscopic treatments, the recurrence of urethral strictures remains a common challenge. Postsurgery pharmacotherapy targeting tissue fibrosis is a promising option for reducing recurrence rates. Although drugs cannot replace surgery, they can be used as adjuvant therapies to improve outcomes. In this regard, many drugs have been proposed based on the mechanisms underlying the pathophysiology of urethral stricture. Ongoing studies have obtained substantial progress in treating urethral strictures, highlighting the potential for improved drug effectiveness through appropriate clinical delivery methods. Therefore, this review summarizes the latest researches on the mechanisms related to the pathophysiology of urethral stricture and the drugs to provide a theoretical basis and new insights for the effective use and future advancements in drug therapy for urethral stricture.

Figure 1

The pathophysiology and related signaling pathway of urethral stricture. (a) The pathology process of urethral stricture. Left: after urinary epidermal injury, platelets and erythrocytes secrete large amounts of cytokines and recruit macrophages (Mφ); middle: macrophages secrete cytokines such as TGF, which promote massive proliferation of fibroblasts and collagen synthesis; right: under the repair action of fibroblasts, collagen is deposited, resulting in epidermal bulging and impaired epidermal elasticity. (b) Role of TGF-β in urethral stricture. TGF-β activation via type I receptors promotes inflammation and progression through the TGF-β/Smads pathway, RhoA/ROCK pathway, Akt/mTOR pathway, and Wnt/β-catenin pathway, promoting the conversion of fibroblasts into myofibroblasts and activating autophagy through epigenetic mechanisms to amplify the profibrotic effects, which together promote urethral stricture formation. RBC: red blood cell; TGF: transforming growth factor; mTOR: mammalian target of rapamycin; RhoA: ras homolog family member A; ROCK: Rho-associated protein kinase; Wnt: wingless/integrated; MLC: myosin light chain; LIMK1: LIM kinase 1; mTORC1: mTOR complex 1; TCF: T cell factor 1; LEBF: lymphoid enhancer factor; MYST: MOZ, Ybf2/Sas3, Sas2, and Tip60; P70S6K: protein 70 S6 kinase.

Figure 2

The PRISMA flowchart. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.