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Updated: Jun 6, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

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Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family

H Michael Shepard1, Cathleen M Brdlik, Hans Schreiber

  • 1Receptor BioLogix, Inc., Palo Alto, California 94303, USA. hms@rblx.com

The Journal of Clinical Investigation
|November 5, 2008
PubMed

Insights

Monoclonal antibodies targeting the human epidermal growth factor receptor (HER) family disrupt cancer cell communication. Future therapies may enhance efficacy by blocking stromal support and HER family signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The human epidermal growth factor receptor (HER) family plays a crucial role in epithelial cancer cell communication with the tumor microenvironment.
  • HER-targeted therapies have shown significant clinical success in treating various epithelial cancers.

Purpose of the Study:

  • To propose a mechanism explaining the success of HER family-targeted monoclonal antibodies in cancer therapy.
  • To suggest future directions for improving HER-targeted cancer therapeutics.

Main Methods:

  • The study proposes a theoretical framework based on existing knowledge of receptor signaling pathways.
  • It extrapolates potential therapeutic strategies from the proposed mechanism.

Main Results:

  • HER family-targeted monoclonal antibodies likely succeed by interfering with the consolidation of signals from other receptor systems.
  • These systems include cytokine receptors, chemokine receptors, Toll-like receptors (TLRs), G protein-coupled receptors (GPCRs), and integrins.

Conclusions:

  • Improvements in HER-targeted cancer therapeutics may involve blocking or reversing stromal support.
  • Isolating the HER family from autocrine and stromal influences is a potential strategy to enhance treatment efficacy.

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