Off-target drug repurposing for rare and ultra-rare cancers: towards a scalable therapeutic framework.

Off-target drug repurposing may provide a scalable therapeutic framework for rare cancers lacking canonical targets, with emerging evidence supporting its potential.

• Why it matters: Limited standard-of-care options and sparse validated models hinder traditional drug repurposing approaches in rare cancers, creating a critical need for alternative strategies that can be rapidly integrated into clinical practice.
• What they did: The authors review emerging pharmacological evidence and criticisms of low-evidence genomic matching, advocating for prospective clinical trials that incorporate off-target candidates within adaptable, safety-focused frameworks for small, heterogeneous cohorts.
• The result: Implementing rigorous, longitudinal, and orthogonal validation in trial designs could enable safer, more effective off-target therapies, expanding treatment options and evidence generation for rare cancer patients.