Abstract / Summary
Drug repurposing builds on pharmacological and safety information already available for an approved drug, but this advantage requires additional studies to establish the biological effect and related mechanisms of action. We conducted a clinically focused review of non-oncology drugs tested as active cancer treatments in interventional studies from 1 January 2021 to 31 July 2026. Randomized trials, phase II-III studies, biomarker-selected cohorts, and studies reporting pharmacokinetics or human target engagement were prioritized. Despite the large number of registered studies, the landscape is still dominated by early-phase, academically sponsored trials. Several widely studied candidates, including metformin, nelfinavir, disulfiram-copper, losartan, and propofol, were negative in randomized evaluations. Conversely, aspirin reduced recurrence in localised colorectal cancer with alterations in the PI3K gene, whilst pre-operative administration of peritumoural lidocaine was associated with improved disease-free survival and overall survival in a randomised trial of breast cancer. Pharmacological insights related to ascorbate in pancreatic cancer and simvastatin in recurrent small-cell lung cancer yielded promising results. Across drug classes, unsuccessful programs were often limited by inadequate exposure, uncertain tumor penetration, absent pharmacodynamic evidence, heterogeneous patient populations, or weak continuity between exploratory and confirmatory development. Progress will depend on more selective clinical hypotheses, early demonstration of human pharmacology, prospective biomarkers, and clear regulatory ownership.