title: The role of EGFR family inhibitors in muscle invasive bladder cancer: a review of clinical data and molecular evidence.
abstract: OBJECTIVE
  Conventional platinum based chemotherapy for advanced urothelial carcinoma is plagued by common resistance to this regimen. Several studies implicate the EGFR family of RTKs in urothelial carcinoma progression and chemoresistance. Many groups have investigated the effects of inhibitors of this family in patients with urothelial carcinoma. This review focuses on the underlying molecular pathways that lead to urothelial carcinoma resistance to EGFR family inhibitors.
  
  
  METHODS
  We performed a PubMed® search for peer reviewed literature on bladder cancer development, EGFR family expression, clinical trials of EGFR family inhibitors and molecular bypass pathways. Research articles deemed to be relevant were examined and a summary of original data was created. Meta-analysis of expression profiles was also performed for each EGFR family member based on data sets accessible via Oncomine®.
  
  
  RESULTS
  Many clinical trials using inhibitors of EGFR family RTKs have been done or are under way. Those that have concluded with results published to date do not show an added benefit over standard of care chemotherapy in an adjuvant or second line setting. However, a neoadjuvant study using erlotinib before radical cystectomy demonstrated promising results.
  
  
  CONCLUSIONS
  Clinical and preclinical studies show that for reasons not currently clear prior treatment with chemotherapeutic agents rendered patients with urothelial carcinoma with muscle invasive bladder cancer resistant to EGFR family inhibitors as well. However, EGFR family inhibitors may be of use in patients with no prior chemotherapy in whom EGFR or ERBB2 is over expressed.
authors.affiliation: Research Service, Veterans Affairs Northern California Health Care System, Sacramento, California.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Mooso
authors.affiliation: California Northstate College of Pharmacy, Rancho Cordova, California.
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Vinall
authors.affiliation: Research Service, Veterans Affairs Northern California Health Care System, Sacramento, California; Department of Medical Microbiology and Immunology, University of California-Davis, Sacramento, California.
authors.forename: Maria
authors.initials: M
authors.lastname: Mudryj
authors.affiliation: Research Service, Veterans Affairs Northern California Health Care System, Sacramento, California; Department of Urology, University of California-Davis, Sacramento, California.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Yap
authors.affiliation: Department of Urology, University of California-Davis, Sacramento, California. Electronic address: rwdeverewhite@ucdavis.edu.
authors.forename: Ralph W
authors.initials: RW
authors.lastname: deVere White
authors.affiliation: Research Service, Veterans Affairs Northern California Health Care System, Sacramento, California; Department of Biochemistry and Molecular Medicine, University of California-Davis, Sacramento, California; Department of Urology, University of California-Davis, Sacramento, California.
authors.forename: Paramita M
authors.initials: PM
authors.lastname: Ghosh
mesh_terms: D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009130:Muscle, Smooth; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D066246:ErbB Receptors
keywords: EGFR tyrosine kinase inhibitor 324674; antineoplastic agents; drug resistance; neoplasm invasiveness; urinary bladder neoplasms