In this week’s ADC Spotlight, Suhail Ahmed Kabeer Rasheed takes HER3 from “undruggable” to centre stage as one of oncology’s most compelling ADC targets. From EGFR‑mutant NSCLC to HR+/HER2– and triple‑negative breast cancer, HER3‑directed ADCs are showing that you don’t need kinase activity to create a therapeutic vulnerability, you need the right combination of epitope, DAR, bystander effect, Fc engineering, and payload class. This article walks through how patritumab deruxtecan opened the door, why TOP1 cross‑resistance is forcing a rethink of deruxtecan‑based designs, and how next‑generation agents like AMT‑562, DB‑1310, HMBD‑501 and bispecific EGFR×HER3 ADCs are rewriting the rules of target selection, sequencing, and biomarker strategy for HER3.
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