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Pathway-driven target prioritisation in drug discovery.

Polina Rusina·David Ochoa·Franck Rapaport·Shameer Khader·Ellen M McDonagh
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Abstract

Genome-scale association studies and functional screens routinely implicate hundreds of candidate genes per disease, yet only a few will be clinically validated as drug targets. Choosing which to pursue is a central drug-discovery decision that depends on interpreting each candidate in its biological context. Curated pathway databases provide this context, while enrichment analysis applies it at scale, turning gene-level signals from genome-wide association, transcriptomic, proteomic and CRISPR studies into mechanistic hypotheses for prioritisation. This review examines how pathway-based methods inform target prioritisation, the databases and tools available for this purpose, and why pathway co-membership should be viewed as a starting point for validation rather than as evidence of causal involvement.

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Polina Rusina, David Ochoa, Franck Rapaport, Shameer Khader, Ellen M McDonagh. 2026-09-16. Pathway-driven target prioritisation in drug discovery.. https://doi.org/10.1016/j.drudis.2026.104805

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