A place for precision medicine in bladder cancer: targeting the FGFRs

Future Oncol. 2016 Oct;12(19):2243-63. doi: 10.2217/fon-2016-0042. Epub 2016 Jul 6.

Abstract

Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients.

Keywords: FGFR1; FGFR3; FGFRs; bladder; cancer; targeted therapy; urothelial.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers
  • Drug Evaluation, Preclinical
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / chemistry
  • ErbB Receptors / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ligands
  • Molecular Targeted Therapy*
  • Mutation
  • Neoplasm Staging
  • Patient Outcome Assessment
  • Patient Selection
  • Precision Medicine* / methods
  • Prognosis
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Signal Transduction / drug effects
  • Translocation, Genetic
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Ligands
  • ErbB Receptors
  • FGFR1 protein, human
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 3