The Role of EGFR Family Inhibitors in Muscle Invasive Bladder Cancer: A Review of Clinical Data and Molecular Evidence

Benjamin A. Mooso, Ruth Louise Vinall, Maria Mudryj, Stanley Yap, Ralph W deVere White, Paramita M Ghosh

Research output: Contribution to journalReview article

36 Scopus citations

Abstract

Purpose 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. Materials and 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.

Original languageEnglish (US)
Pages (from-to)19-29
Number of pages11
JournalJournal of Urology
Volume193
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • antineoplastic agents
  • drug resistance
  • EGFR tyrosine kinase inhibitor 324674
  • neoplasm invasiveness
  • urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

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