In a prospective multicenter evaluation, researchers used genomics-guided off-label precision therapies under the Dutch Drug Rediscovery Protocol (DRUP) to identify molecular subgroups with substantial benefit. DRUP enrolled 1,610 patients with advanced or metastatic solid tumors after standard options were exhausted. The report, published in Nature, describes a staged design that escalates cohorts only when clinical benefit is observed. The investigators emphasized frameworks that systematically evaluate efficacy and toxicity, refine biomarkers, and use regulatory-aligned endpoints to support future label expansion. The approach aims to balance repurposing potential against patient risk from off-label use, while generating evidence that can inform label-level decisions. The work also underscores the value of biomarker refinement using outcome data captured prospectively rather than relying on retrospective signals. For the biotech and pharma pipeline, DRUP strengthens the case that genomics-guided off-label prescribing—when structured—can deliver actionable subgroup evidence that may later support regulatory expansion.