Figure 3.

Schema of ERBB2. (A): The G660D mutation is located in the ERBB2 transmembrane domain. Other missense or in‐frame mutations are also shown. The MEK/ERK signaling pathway is stimulated by dimerization of ERBB2. (B): Mechanisms of monoclonal antibodies, such as trastuzumab, and tyrosine kinase inhibitors (TKIs), such as afatinib, for ERBB2. Trastuzumab and other monoclonal antibodies bind to the ECD and prevent dimerization of ERBB2, whereas afatinib and other TKIs bind to the kinase domain (KD) and inhibit ERBB2. The KD is activated in ERBB2 KD‐ or TMD‐mutant tumors regardless of ECD status.

Abbreviations: ECD, extracellular domain; ERBB2, avian erythroblastic leukemia viral oncogene homolog 2 (erb‐b2 receptor tyrosine kinase 2); ERK, extracellular signal‐regulated kinases; MEK, MAPK‐ERK kinase; Mut, mutation; RAF, rapidly accelerated fibrosarcoma proto‐oncogene, serine/threonine kinase; RAS, rat sarcoma viral oncogene homolog; TMD, transmembrane domain.