Bladder neoplasms and NF-κB: an unfathomed association.

Introduction: Bladder cancer is the second most common genitourinary tract cancer and is often recurrent and/or chemoresistant after tumor resection. Cigarette smoking, exposure to aromatic amines, and chronic infection/inflammation are bladder cancer risk factors. NF-κB is a transcription factor that plays a critical role in normal physiology and bladder cancer. Bladder cancer patients have constitutively active NF-κB triggered by pro-inflammatory cytokines, chemokines, and hypoxia, augmenting carcinogenesis and progression.Areas covered: NF-κB orchestrates protein interactions (PTEN, survivin, VEGF), regulation (CYLD, USP13) and gene expression (Trp 53) resulting in bladder cancer progression, recurrence and resistance to therapy. This review focuses on NF-κB in bladder inflammation, cancer and resistance to therapy.Expert opinion: NF-κB and bladder cancer necessitate further research to develop better diagnostic and treatment regimens that address progression, recurrence and resistance to therapy. NF-κB is a master regulator that can act with or on minimally one cancer hallmark gene or protein, leading to bladder cancer progression (Tp53, PTEN, VEGF, HMGB1, CYLD, USP13), recurrence (PCNA, BcL-2, JUN) and resistance to therapy (P-gp, twist, SETD6). Thus, an understanding of bladder cancer in relation to NF-κB will offer improved strategies and efficacious targeted therapies resulting in minimal progression, recurrence and resistance to therapy.

Citation

Charles Emmanuel Jebaraj Walter, Sankari Durairajan, Kalaiselvi Periyandavan, George Priya Doss C, Dicky John Davis G, Hannah Rachel Vasanthi A, Thanka Johnson, Hatem Zayed. Bladder neoplasms and NF-κB: an unfathomed association. Expert review of molecular diagnostics. 2020 May;20(5):497-508

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PMID: 32228251

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