Zanidatamab

HER2 is a receptor tyrosine kinase that, upon activation, triggers the activation of multiple downstream intracellular signaling pathways (such as MAPK) crucial for governing cell proliferation, differentiation, and apoptosis. The activation process relies on dimerization, which is crucial for signal transmission as it activates the tyrosine kinase domain responsible for phosphorylation of intracellular tyrosine residues. Disruption of HER2 function is a contributing factor in a variety of cancers, including biliary tract cancers.

Zanidatamab is a bispecific monoclonal antibody that inhibits HER2 by binding to two distinct extracellular sites: the juxtamembrane domain and dimerization domain. The binding of zanidatamab to HER2 prevents HER2 dimerization and induces cell death following internalization.