Drug Repurposing and Translational Research: Integrating AI, Pharmacogenomics, and Precision Therapeutics

Drug repurposing has emerged as a strategic and cost-effective alternative to conventional de novo drug discovery, offering accelerated therapeutic development by identifying new clinical indications for existing pharmacological agents. The growing complexity of disease biology, coupled with escalating research and development costs and high attrition rates, has necessitated innovative translational approaches that bridge basic science and clinical application. In this context, drug repurposing has evolved from serendipitous discovery to a systematic, data-driven, and translationally informed paradigm. This chapter provides a comprehensive overview of drug repurposing within a translational research framework, emphasizing the integrative roles of artificial intelligence, pharmacogenomics, and precision therapeutics. The conceptual foundations and classification of drug repurposing strategies are discussed, followed by an examination of translational pathways that enable bench-to-bedside-to-bench progression. Advances in AI-driven drug repurposing, including machine learning, deep learning, and network pharmacology approaches, are critically analyzed with illustrative case studies from oncology and infectious diseases. The chapter further explores the impact of pharmacogenomic variability on repurposed drug response, population stratification, and personalized therapeutic decision-making. Clinical successes and failures, including lessons learned from oncology repurposing efforts and the COVID-19 pandemic, are evaluated to highlight key determinants of translational success and late-stage failure. Regulatory pathways, intellectual property considerations, and the growing role of real-world evidence in repurposed drug approval are also examined. Finally, future perspectives are discussed, focusing on the convergence of AI and genomics, emerging digital twin technologies, adaptive clinical trial designs, and unresolved research gaps. Collectively, this chapter positions drug repurposing as a precision-oriented, ethically grounded, and translationally robust strategy for next-generation therapeutic development.