HER3

Class

HER3-directed antibody-drug conjugate (exatecan-derived topoisomerase I inhibitor payload)

Pathway

HER3/ERBB3 signaling

Notes

original target text: HER3 (ERBB3)

HER3 (ERBB3) is a member of the epidermal growth factor receptor (EGFR/HER) family of cell-surface receptors that regulate cell growth and survival. Unlike its relatives EGFR and HER2, HER3 has a catalytically weak (pseudokinase) intracellular domain, so it functions mainly by pairing with other HER-family members, especially HER2, to transmit growth signals into the cell. This partnership strongly activates the PI3K/AKT pathway, a central driver of cell survival and proliferation, and HER3 upregulation is a common route by which tumors resist therapies aimed at EGFR or HER2. Because HER3 itself lacks strong enzymatic activity, it is difficult to block with conventional small-molecule inhibitors, which has favored antibody-based approaches, including antibody-drug conjugates (ADCs) that use a HER3-binding antibody to deliver a cytotoxic payload directly into HER3-expressing cells. This mechanism broadly matters in cancers such as non-small cell lung cancer and breast cancer, particularly in settings where HER3 expression contributes to disease progression or treatment resistance, offering a way to target tumor cells that other HER-directed therapies leave unaffected.