HER Family of Membrane Receptors Tyrosine Kinase Receptor Activity Major Ligands
HER1 (EGFR) Yes EGF, amphiregulin, TGF-a HER2 Yes None HER3 No Heregulin HER4 Yes Heregulin Abbreviations: EGF, epidermal growth factor;EGFR, epidermal growth factor receptor;TGF-a, transforming growth factor a.
Neratinib is an oral, irreversible inhibitor of HER1, HER2 and HER4.
There are also promising results from an ongoing Phase II study of BIBW 2992, another novel, dual inhibitor of HER1 and HER2.
Vandetanib (ZD6474) is a competitive inhibitor at the ATP-binding site of VEGFR-2 and additionally inhibits HER1.
Assessing the quantitative levels of expression and co-expression of
HER1 and HER3 proteins in conjunction with HER2 measurements by HERmark will substantially increase our knowledge of how the expression of these HER-family proteins are represented in breast cancer.
It belongs to a family of four transmembrane tyrosine kinase cell surface receptors which also includes HER1, HER3 and HER4.
Examples of potentially relevant mechanisms include: disruption of the trastuzumab-HER2 interaction which has been demonstrated, for example, to occur by the overexpression of MUC4, a sialomucin complex overexpressed in some breast tumours [49,50]; increased signalling through other members of the HER family, such as HER1, to downstream messenger pathways [51,52]; compensatory signalling through other receptor types such as insulin-like growth factor-I receptor (IGF-IR) which is able to inhibit HER2 sensitivity to trastuzumab through crosstalk [53,54]; or modulation of downstream signalling pathways for example via PTEN deficiency [14] or downregulation of p27(Kip1) [55].
Lapatinib is an orally active selective dual HER1 and HER2 tyrosine kinase inhibitor [concentration giving 50% inhibition (I[C.
Poziotinib is a novel, oral pan-HER inhibitor that irreversibly blocks signaling through the Epidermal Growth Factor Receptor (EGFR, HER) Family of tyrosine-kinase receptors, including
HER1 (erbB1; EGFR), HER2 (erbB2), and HER4 (erbB4), and importantly, also HER receptor mutations; this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors.
