Human epidermal growth factor receptor 2 (HER2) extracellular domain IV and tubulin (HER2 ECD IV / Tubulin)

Human epidermal growth factor receptor 2 (HER2) extracellular domain IV and tubulin represent a dual-target system utilized by antibody-drug conjugates (ADCs) like trastuzumab emtansine to treat HER2-positive malignancies. HER2 is a transmembrane receptor tyrosine kinase that drives cell growth and survival; its overexpression is a key oncogenic driver in breast and gastric cancers (Cho et al., Nature, 2003). Domain IV of the HER2 extracellular domain is the specific epitope recognized by the monoclonal antibody trastuzumab, which facilitates receptor-mediated endocytosis (LoRusso et al., Clinical Cancer Research, 2011). Tubulin is a structural protein that polymerizes into microtubules, which are essential for forming the mitotic spindle during cell division (Jordan & Wilson, Nature Reviews Cancer, 2004). Once the ADC is internalized and degraded in lysosomes, the cytotoxic payload (e.g., DM1) is released and binds to tubulin, inhibiting microtubule assembly and inducing mitotic arrest and apoptosis (FDA Label, Kadcyla). This mechanism allows for the selective delivery of potent chemotherapy to HER2-overexpressing cells while sparing healthy tissues that lack high HER2 expression.

Other names

ErbB2CD340NeuProto-oncogene NeuTubulin alphaTubulin beta

Antibody-drug conjugate (ADC) targeting of HER2 ECD IV followed by intracellular tubulin inhibition