EGFR + HER3

Class

EGFR/HER3 bispecific antibody-drug conjugate

Pathway

dual blockade of EGFR-HER3 co-signaling (proliferation, survival, migration, angiogenesis) plus cytotoxic payload delivery; HER3 co-targeting intended to overcome EGFR-inhibitor resistance

EGFR (epidermal growth factor receptor) and HER3 (human epidermal growth factor receptor 3) are cell-surface receptor tyrosine kinases belonging to the ErbB family, which drive cell proliferation, survival, and migration when activated by growth factor ligands. Many solid tumors depend on excessive signaling through these receptors, and EGFR alone has long been a validated target for antibodies and small-molecule inhibitors. However, tumors frequently develop resistance to EGFR-directed therapy by upregulating HER3 or its signaling partners, restoring downstream proliferative and survival signals. A bispecific antibody that engages both EGFR and HER3 simultaneously blocks this compensatory escape route while also bringing the two receptors into closer physical proximity, which can enhance receptor internalization. In the antibody-drug conjugate format, this dual-targeting antibody additionally serves as a delivery vehicle: after binding, the complex is internalized and releases a cytotoxic payload directly inside the tumor cell, combining pathway blockade with direct cell killing. This approach is relevant across epithelial cancers where EGFR and HER3 co-expression contributes to tumor growth and to resistance against earlier-generation EGFR inhibitors, offering a way to address both the signaling dependency and the acquired resistance mechanisms that limit single-target agents.