Moving Tumor-Agnostic Therapy to the Big Stage: Translational and Molecular Oncology Highlights from the ESMO Congress 2025.

The ESMO Congress 2025 in Berlin marked a milestone in precision oncology with the introduction of the first dedicated tumor-agnostic track, reflecting the shift from organ-based to molecularly defined cancer therapy. Across multiple sessions, updated data on biomarker-driven and pathway-based treatments demonstrated how targeted therapies can transcend histologic boundaries. Highlights included long-term results for approved tumor-agnostic agents (e.g., NTRK and BRAF-directed therapies, HER2-targeted antibody-drug conjugates [ADCs], as well as next-generation KRAS inhibitors, HER2- and TROP2-directed tyrosine kinase inhibitors and ADCs, and novel targets such as MTAP deletions, MET amplification, CD44v9 and MUC1. In parallel, advances in synthetic-lethality strategies beyond PARP inhibition and the clinical implementation of ctDNA-based minimal-residual-disease monitoring showcased how molecular profiling and liquid biopsies are reshaping treatment selection and response assessment. Taken together, these developments highlight the growing momentum in biomarker-guided and molecularly driven cancer care.