This article details a translational study that investigates the spatial determinants of the efficacy of the antibody-drug conjugate (ADC) SHR-A1811 in HER2-positive breast cancer patients receiving neoadjuvant treatment. The research integrates multi-omics data, including DNA/RNA sequencing and advanced spatial analysis techniques like computational pathology and Xenium in situ imaging. Key findings suggest that biomarkers predicting treatment response vary by hormone receptor (HR) status: HR-negative tumors respond better with high infiltration and tight interaction of cytotoxic T cells, while HR-positive tumors show a poorer response when HER2-strong-positive tumor cells are spatially aggregated. Ultimately, the authors developed a predictive model leveraging these spatial and clinicopathological features to forecast the efficacy of SHR-A1811 and similar novel ADCs.

References:

• Ma D, Dai L J, Wu X R, et al. Spatial determinants of antibody-drug conjugate SHR-A1811 efficacy in neoadjuvant treatment for HER2-positive breast cancer[J]. Cancer Cell, 2025, 43(6): 1061-1075. e7.