ERBB2 (HER2), including genetic alterations and wild-type overexpression

Class

Oral ATP-competitive covalent ERBB2 (HER2) tyrosine kinase inhibitor, CNS-penetrant

Pathway

Covalently inhibits ERBB2 kinase activity while sparing EGFR wild-type

ERBB2, commonly called HER2, is a receptor tyrosine kinase belonging to the epidermal growth factor receptor (EGFR) family, a group of proteins embedded in the cell membrane that transmit growth signals from outside a cell to its interior. HER2 lacks a known natural ligand and instead acts by pairing with other family members, particularly EGFR and HER3, to activate intracellular signaling cascades such as RAS/MAPK and PI3K/AKT that drive cell division and survival. In many cancers, the ERBB2 gene is amplified or overexpressed, or carries activating mutations, producing constant growth signaling that supports tumor formation and spread. This occurs across breast, gastric, and lung cancers, among others. Because HER2 activity is a direct oncogenic driver in these settings, agents that inhibit its kinase function can slow or halt tumor growth. This particular mechanism is designed as an orally available, ATP-competitive small molecule that binds the kinase's active site and forms a covalent, essentially permanent bond, while sparing wild-type EGFR to reduce off-target effects linked to that closely related receptor. Its capacity to cross the blood-brain barrier is relevant because HER2-driven tumors frequently spread to the brain.