Pertuzumab binds to HER2, the most common HER pairing partner, at the dimerization domain [ 79], inhibiting its ability to form dimers with other HER receptors [ 80, 81].
It binds to the dimerization site on the HER2 domain and prevents ligand-driven pairing of HER2 with other HER receptors, thus inhibiting tumor cell growth and survival.
Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER-2 receptor and inhibits its ability to dimerize with other HER receptors blocking the cell growth, signaling and apoptosis induction.
As HER2 is the preferred dimerization partner for EGFR and other HER receptors, we proceeded to determine the effect of TKIs on HER2 phosphorylation state induced through other HER receptors under various conditions.
To establish an assay for HER2 phosphorylation state, it was necessary to trigger HER2 phosphorylation via other HER receptors.
However, it does not have an intrinsic kinase activity, and has to relay on a heterodimeric partnership with other HER family members for signal transduction.
To resolve the controversy, we used FRET to study activation changes in HER2 and other HER receptors in relationship to TKIs treatment in breast cancer cell lines.
Studies on small series of penile cancer show frequent overexpression of EGFR, but there is no data on other HER receptors in penile cancer [18], [19].
HER-2 is the preferred dimerization partner for the other HER members [ 32].
