A Dutch multicenter team reported responses to off-label genomics-guided targeted drugs and immunotherapies through the prospective DRUP protocol, identifying molecular subgroups with “substantial benefit.” The findings were published in Nature and focused on advanced solid tumor patients who had exhausted standard-of-care options. Investigators tracked outcomes in 1,610 individuals using a staged design that expands cohorts only after observing sufficient clinical benefit, with formal emphasis on high-confidence targets and toxicity monitoring. The authors argued that off-label precision should operate within frameworks that systematically capture efficacy and safety to support biomarker refinement and potential label expansion. The DRUP results provide evidence for a structured way to extend approved therapies to genetically matched populations while managing regulatory and ethical concerns around off-label use.