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Focus on HER1/EGFR as a therapeutic target

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Strategies for targeting HER1/EGFR

Strategies for targeting HER1/EGFR
HER1/EGFR contains both an extracellular ligand-binding domain and an intracellular tyrosine kinase domain, which is activated to initiate multiple downstream signaling pathways.2,3,22 Therefore, HER1/EGFR can be targeted in several ways.

HER1/EGFR is a potential therapeutic target

The association of HER1/EGFR with lung and pancreatic cancers makes it a potential therapeutic target in those tumor types. There are several possible ways to target HER1/EGFR.

Targeting HER1/EGFR ligands

Several ligands, such as TGF-α and EGF, bind HER1/EGFR.1 These ligands could be potential therapeutic targets.

  • Molecules such as monoclonal antibodies would bind to HER1/EGFR ligands, preventing them from binding to HER1/EGFR
    • HER1/EGFR has several receptor-specific ligands1

Targeting the ligand-binding domain of HER1/EGFR

The extracellular domain of HER1/EGFR, which binds ligands, is another possible therapeutic target.1,2

  • Molecules such as monoclonal antibodies would bind to the extracellular domain of HER1/EGFR to suppress its activity2
    • In theory, this would prevent activation of the tyrosine kinase domain of HER1/EGFR

Targeting the intracellular domain of HER1/EGFR

The tyrosine kinase domain of HER1/EGFR is located within the cell membrane and also represents a potential therapeutic target.1

  • Small molecules can prevent transphosphorylation and activation of the tyrosine kinase domain of HER1/EGFR1
    • Without activation of the tyrosine kinase domain of wild-type HER1/EGFR, downstream signaling pathways cannot be initiated2
    • Clinical research indicates that the level of HER1/EGFR phosphorylation is linked to prognosis, making this target of particular interest10

Targeting downstream signaling pathways

HER1/EGFR-containing dimers initiate a number of downstream signaling pathways.2 Molecules within these pathways could also be potential therapeutic targets.

  • Because HER1/EGFR dimers induce multiple signaling pathways,1 each pathway might require a different molecule for therapeutic inhibition

 

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