Bridging the Divide: Mechanistic Insights Into Non-Oncology Drug Repurposing for Cancer and Neurodegeneration

For incurable illnesses like cancer and neurodegeneration, strategic alternatives are required because the traditional drug development pipeline is marked by huge expenses, longer timelines, and high failure rates. By utilizing the proven safety profiles of authorized non-oncology medications, pharmacological repurposing (DRP) presents a promising avenue. However, switching from accidental discovery to mechanism-driven validation is crucial to this strategy's success. This review offers a thorough mechanistic analysis of DRP candidates (old drugs), emphasizing medications that take advantage of the convergent pathophysiology of neurological decline and cancer by acting through non-canonical targets. We describe how common drugs, such as the cholesterol-lowering Statins and the anti-diabetic Metformin, have anti-cancer and neuroprotective effects by specifically altering common cellular markers. The Mevalonate pathway, autophagy/lysosomal dysfunction (e.g., by anti-infectives), the non-metabolic targeting of AMPK/mTOR signaling, and the complex interactions with the tumor and neuro-inflammatory microenvironments are some of the important mechanisms that are addressed.Using particular clinical trials for high-priority drugs like metformin and mebendazole in oncology, we examine the translational status of these candidates. We conclude by addressing the systemic issues, suggesting that the successful matching of current medications to new, complex disease signatures will depend on resolving intellectual property challenges, improving clinical trial design, and incorporating computational strategies (such as AI-driven network pharmacology). DRP can hasten the delivery of safe, efficient treatments to patients with unmet clinical needs by giving priority to the elucidation of novel mechanisms.