Bladder neoplasms and NF-κB: an unfathomed association

Expert Rev Mol Diagn. 2020 May;20(5):497-508. doi: 10.1080/14737159.2020.1743688. Epub 2020 Apr 12.


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.

Keywords: Bladder cancer; NF-κB; chemoresistance; inflammation; signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers
  • Carrier Proteins
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Disease Management
  • Disease Progression
  • Disease Susceptibility*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Protein Binding
  • Signal Transduction
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / etiology*
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / therapy


  • Biomarkers
  • Carrier Proteins
  • NF-kappa B