Biomarkers of Drugs Targeting HER-family Signalling in Cancer

J Pathol. 2014 Jan;232(2):219-29. doi: 10.1002/path.4269.

Abstract

The epidermal growth factor receptor family (EGFR/HER) is frequently deregulated in human cancers. Several aberrations at various levels have been successfully exploited as targets for anti-cancer therapies. However, with very few exceptions, drugs targeting HER signalling have shown only modest activity when used alone in cancers where a HER-related target can be identified. Optimization of the use of these drugs either alone or in combination with other anti-cancer agents would require a more precise definition of alterations that could predict for activity or resistance. Clinical validation of the several potential biomarkers emerging from clinical and translational studies is a challenging process. Thanks to combined efforts, collection of tumour tissues and other potentially relevant patients' materials has become more and more frequently mandatory in prospective studies with biologically targeted therapies. As a consequence, information on the value of promising biomarkers of drugs targeting HER-family receptor targeting is becoming available. This review will focus on breast cancer, where the HER2 subset has been the subject of a major research effort in the last two decades, and on gastric cancer, where HER2 targeting has emerged recently as a successful strategy.

Keywords: HER1/EGFR; HER2/neu; HER3; biologically targeted therapy; biomarker; breast cancer; gastric cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Drug Discovery*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Male
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-3 / antagonists & inhibitors
  • Receptor, ErbB-3 / metabolism
  • Signal Transduction / drug effects*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ERBB2 protein, human
  • ERBB3 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3