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Pharmacogenomic Stratification for Oncology Drug Repurposing: An Exposure Target Context Eligibility Framework
Mohamed El-Tanani1, Adil Farooq Wali1, Syed Arman Rabbani1
1RAK College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates.
Pharmaceuticals (Basel, Switzerland)
|June 26, 2026
Summary
Drug repurposing trials often fail due to lack of pharmacogenomic criteria. The proposed Pharmacogenomic Stratification Framework for Drug Repurposing (PSDR) integrates exposure, target, and context to improve oncology trial design and success rates.
Area of Science:
- Oncology
- Pharmacogenomics
- Drug Development
Background:
- Most oncology drug repurposing trials lack efficacy.
- Potential causes include dosing, trial design, and patient diversity issues.
- Absence of pharmacogenomic eligibility criteria is a major contributor to trial failure.
Purpose of the Study:
- To propose the Pharmacogenomic Stratification Framework for Drug Repurposing (PSDR).
- To offer a novel framework for predicting drug response in oncology.
- To guide biomarker-stratified clinical trial design for repurposed agents.
Main Methods:
- The PSDR framework integrates Exposure (pharmacokinetic adequacy), Target engagement (somatic tumor genomics), and Context competence (tumor microenvironment).
- A conceptual model R = E × T × C is proposed for drug activity.
- Five pharmacogenomic hypotheses for common drugs were derived, along with a scoring system.
Main Results:
- The PSDR model provides necessary, though not sufficient, conditions for anticancer drug activity.
- Five testable hypotheses for metformin, statins, beta-blockers, NSAIDs, and SSRIs were generated.
- A three-point PSDR eligibility scoring system was proposed.
Conclusions:
- The PSDR framework complements existing precision oncology resources.
- Prospective validation in stratified cohorts is required for clinical implementation.
- PSDR-guided enrichment designs could enhance repurposing trial efficiency and interpretability.
Keywords:
ADMEPSDRR = E × T × Cdrug repurposingpharmacogenomicsprecision oncologypredictive biomarkerstumor microenvironmentMore Related Videos
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