HER3, serious partner in crime Therapeutic approaches and potential biomarkers for effect of HER3-targeting

Arjan Kol, Anton Terwisscha Van Scheltinga, Hetty Timmer-Bosscha, Laetitia E. Lamberts, Frederike Bensch, Elisabeth de Vries, Carolina P. Schroder*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

58 Citations (Scopus)

Abstract

The human epidermal growth factor receptor (HER) family members are targeted by a growing numbers of small molecules and monoclonal antibodies. Resistance against the epidermal growth factor receptor (EGFR) and HER2-targeting agents is a clinically relevant problem forcing research on optimizing targeting of the HER family. In view of its overexpression in tumors, and compensatory role in HER signaling, HER3 has gained much interest as a potential additional target within the HER family. It is the only member of the HER family lacking intrinsic tyrosine kinase activity and therefore its role in cancer has long been underestimated. Drugs that block HER3 or interfere with HER3 dimer signaling, including fully human anti-HER3 antibodies, bispecific antibodies and tyrosine kinase inhibitors (TKIs), are currently becoming available. Several compounds have already entered clinical trial. In the meantime potential biomarkers are tested such as tumor analysis of HER3 expression, functional assays for downstream effector molecules and molecular imaging techniques. This review describes the biology and relevance of HER3 in cancer, agents targeting HER3 and potential biomarkers for effect of HER3-targeting. (C) 2014 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalPharmacology & Therapeutics
Volume143
Issue number1
DOIs
Publication statusPublished - Jul-2014

Keywords

  • HER3
  • Molecular imaging
  • Biomarkers
  • Monoclonal antibodies
  • Tyrosine kinase inhibitors
  • Resistance
  • EPIDERMAL-GROWTH-FACTOR
  • METASTATIC BREAST-CANCER
  • C-ERBB-3 PROTEIN EXPRESSION
  • RESISTANT OVARIAN-CANCER
  • FACTOR RECEPTOR FAMILY
  • AFATINIB BIBW 2992
  • TYROSINE KINASE
  • EGF RECEPTOR
  • CELL-PROLIFERATION
  • ANTITUMOR-ACTIVITY

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