Antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (T-DXd, Enhertu) have transformed HER2-expressing breast cancer therapy, yet clinical benefit remains unpredictable and current IHC/FISH diagnostics fail to capture the molecular context governing ADC sensitivity. To address this, we developed Genialis adcID, an RNA-based survival model built on the Genialis Supermodel — a foundation model that maps gene expression into biomodules representing key oncologic hallmarks including ADC mechanism-relevant biology. Applied to a real-world patient cohort, the model identifies transcriptomic patterns associated with T-DXd response that go beyond target expression, revealing biological programs linked to DNA damage response, stress signaling, and hormone regulation.

Published for AACR 2026.