Strategic Approaches to Drug Repurposing In Complex Diseases

Drug repurposing — the systematic identification of new therapeutic applications for
approved or investigational compounds — has emerged as a transformative strategy in
modern pharmaceutical development, reducing development costs by 60–85% and timelines
by half compared to de novo drug discovery. This chapter provides a comprehensive
examination of the strategic landscape of drug repurposing in complex diseases,
encompassing four major methodological pillars: computational approaches (network
pharmacology, molecular docking, AI/machine learning, transcriptomics via the
Connectivity Map, and phenome-wide association studies), experimental phenotypic
screening, target-based strategies, and clinical epidemiology. Applications across oncology,
neurodegeneration, cardiovascular disease, and rare and neglected diseases are analyzed in
depth, with detailed case studies of landmark repurposing successes including thalidomide
for multiple myeloma, sildenafil for Alzheimer's disease, colchicine for secondary
cardiovascular prevention, baricitinib for COVID-19, and rituximab for autoimmune
conditions. The chapter critically examines persistent structural barriers — intellectual
property gaps, commercial disincentives, translational failures, and trial design challenges —
and presents emerging frontiers in AI-driven discovery, multi-omics integration, patient
derived organoid screening, and open-science platforms. Drug repurposing represents one of
the most efficient pathways to addressing the 90% of human diseases still lacking effective
treatment options.