Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification

J Clin Oncol. 2006 Dec 10;24(35):5552-64. doi: 10.1200/JCO.2006.08.2073.


Papillary and invasive cancers of the urinary bladder appear to evolve and progress through distinct molecular pathways. Invasion in bladder cancer forebodes a graver prognosis, and these tumors are generally characterized by alterations in the p53 and retinoblastoma (RB) pathways that normally regulate the cell cycle by interacting with the Ras-mitogen activated protein kinase signal transduction pathway. Tumor angiogenesis further contributes to the neoplastic growth by providing a constant supply of oxygen and nutrients. Distinct epigenetic and genetic events characterize the interplay between the molecules involved in these pathways, thus affording their use as indicators of prognosis. Efforts are now underway to construct molecular panels comprising multiple markers that can serve as more robust predictors of outcome. While clinical trials for targeted chemotherapy for bladder cancer have commenced, novel genetic and pharmacologic agents that can target pathway-specific molecules are currently under development. The next generation of clinical management for urothelial carcinoma will witness the use of multimarker panels for prognostic prediction and combination therapy directed at novel molecular targets for treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Disease Progression
  • Humans
  • MAP Kinase Signaling System
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / pathology
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Urinary Bladder Neoplasms / blood supply
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*
  • ras Proteins / genetics
  • ras Proteins / metabolism


  • Retinoblastoma Protein
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ras Proteins