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Mechanisms of resistance to HER family targeting antibodies

Tim J Kruser1, Deric L Wheeler

  • 1Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.

Experimental Cell Research
|January 13, 2010
PubMed

Insights

Resistance to antibody therapies targeting the epidermal growth factor receptor (EGFR) and HER2 in cancer is common. This review explores resistance mechanisms and strategies to overcome them for improved HER family therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The epidermal growth factor (EGF) family, including EGFR and HER2, plays a crucial role in epithelial cancers.
  • Aberrant EGFR and HER2 signaling drives proliferation, angiogenesis, invasion, and metastasis in various cancers like NSCLC, CRC, and breast cancer.
  • Targeted therapies like monoclonal antibodies (e.g., cetuximab, trastuzumab) and small molecules (e.g., erlotinib) inhibit EGFR/HER2 activity with clinical promise.

Purpose of the Study:

  • To review mechanisms of resistance to antibody-based therapies targeting EGFR and HER2.
  • To identify similarities in resistance profiles between EGFR and HER2 antibody therapies.
  • To discuss strategies for overcoming resistance to HER family-targeting monoclonal antibody therapy.

Main Methods:

  • Literature review of studies on EGFR and HER2 antibody resistance.
  • Analysis of clinical and preclinical data on therapeutic resistance mechanisms.
  • Comparative analysis of resistance profiles across different HER family antibodies.

Main Results:

  • While tyrosine kinase inhibitor resistance is well-studied, resistance to monoclonal antibodies against EGFR/HER2 is less understood.
  • A significant proportion of patients do not respond to or become refractory to antibody-based therapies.
  • Similarities exist in resistance mechanisms to antibodies targeting EGFR and HER2.

Conclusions:

  • Understanding resistance to EGFR and HER2 antibody therapies is critical for improving patient outcomes.
  • Developing strategies to overcome resistance is essential for effective HER family-targeted cancer treatment.
  • Further research is needed to elucidate and address antibody resistance mechanisms in clinical settings.

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