Cancer Drug Repurposing: Pathophysiology, Therapeutic Targeting and Translational Opportunities

Abstract

Cancer remains a major global health challenge because of its biological complexity, marked genomic instability, tumor heterogeneity, metastatic potential, and the frequent emergence of resistance to anticancer treatment. The conventional discovery and development of new medicines is lengthy, expensive, and associated with substantial attrition during clinical development. These limitations have stimulated increasing interest in drug repurposing, a strategy in which an established medicine is investigated for a new therapeutic indication. Repurposing can exploit existing pharmacokinetic, pharmacodynamic, toxicological, manufacturing, and clinical information, potentially shortening the path from laboratory investigation to clinical evaluation. The present review integrates the major biological features of cancer with therapeutic targeting and the potential role of repurposed medicines in oncology. It discusses cancer etiology and pathophysiology, genetic and epigenetic alterations, tumor heterogeneity, cancer stem cells, tumor–stroma interactions, invasion and metastasis, and the molecular basis of therapeutic resistance. Selected examples of medicines investigated for anticancer applications—including metformin, celecoxib, mesalamine, epirubicin, quinacrine, levofloxacin, 5-fluorouracil, doxorubicin, paclitaxel, and ketoconazole—are considered in the context of the original manuscript. The review also addresses repurposing opportunities involving psychiatric medicines and radiotherapy-associated strategies. Overall, drug repurposing represents a complementary approach rather than a substitute for conventional drug discovery. Its future success will depend on robust mechanistic validation, biomarker-guided patient selection, appropriate dose optimization, well-designed clinical trials, and careful evaluation of efficacy, safety, and drug–drug interactions.