OncoAlert 4Sight Abstracts to be Presented at #ESMO26
Paired-Biopsy Multi-Omic Analysis Reveals Target-Independent Mechanisms of Antibody–Drug Conjugate (ADC) Resistance in Metastatic Breast Cancer (MBC)

🎙️ @PTarantinoMD
🔬 Paired-biopsy multi-omic study (n=26): pre-treatment vs post-progression MBC biopsies after T-DXd, sacituzumab govitecan, or both. #BreastCancer

➡️ T-DXd: HER2 decreased in 57%, but none became HER2-null
➡️ SG: no consistent TROP2 downregulation (5/14 up, 3/14 down)
➡️ >50% had increased efflux transporters (ABCB1, ABCC1); functional validation showed reduced payload accumulation and ADC sensitivity
✅ ADC resistance appears driven by complex adaptations beyond target modulation, highlighting drug efflux, trafficking and cellular stress responses.

(4Sight Made from Abstracts publicly available at the ESMO website)

@matteolambe @aftimosp @E_de_Azambuja @DrSGraff @ErikaHamilton9 @double_whammied @maryam_lustberg @raalbany @hoperugo @stolaney1 @LoiSher @SirohiBhawna @jamecancerdoc @JavierCortesMD @JaniceTNBCmets @Prof_Nadia_H