EGFR / HER3 (ERBB3) dual

Class

Bispecific antibody-drug conjugate (EGFR/HER3, topoisomerase I payload, DualityBio bispecific ADC platform)

Pathway

Simultaneously engages EGFR and HER3, frequently co-expressed in aggressive solid tumors, delivering a topoisomerase I payload upon internalization

EGFR (epidermal growth factor receptor) and HER3 (ERBB3) belong to the ERBB family of receptor tyrosine kinases that relay growth and survival signals into cells. Many aggressive solid tumors express both receptors together: EGFR drives proliferation, while HER3, despite weak catalytic activity on its own, amplifies survival signaling through partnering with other ERBB family members and often allows tumors to bypass therapies aimed at EGFR alone. An antibody engineered to bind both receptors at once can identify tumor cells more selectively than an antibody against either target individually, since co-expression is more specific to malignant tissue, and dual binding also promotes more efficient receptor clustering and uptake into the cell. This bispecific antibody is used here as a delivery vehicle in an antibody-drug conjugate: a chemical linker attaches a DNA-damaging payload (a topoisomerase I inhibitor) to the antibody. After the antibody binds and is internalized, the payload is released inside the cell, blocking DNA replication and causing cell death; some released payload can also diffuse into neighboring tumor cells regardless of their own receptor levels. This approach is relevant to solid tumors marked by EGFR/HER3 co-expression, including those no longer responsive to conventional EGFR-targeted treatment.