Targeting Epidermal Growth Factor Receptor in triple negative breast cancer: New discoveries and practical insights for drug development

Cancer Treat Rev. 2017 Feb:53:111-119. doi: 10.1016/j.ctrv.2016.12.010. Epub 2017 Jan 5.

Abstract

Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor+ and HER2+ breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epidermal Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC.

Keywords: Epidermal Growth Factor Receptor; Targeted therapy; Triple negative breast cancer; mTOR.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Cetuximab / therapeutic use
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Immunotherapy / methods
  • Molecular Targeted Therapy / methods
  • Panitumumab
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-met / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / genetics

Substances

  • Antibodies, Monoclonal
  • Protein Kinase Inhibitors
  • Panitumumab
  • MTOR protein, human
  • EGFR protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Cetuximab