Drug repurposing in oncology: a path beyond the bottleneck.

Cancer is a major worldwide health burden, with rising incidence and mortality rates highlighting the critical need for more effective and accessible treatment alternatives. Conventional drug development is often hindered by long timelines, high prices, and significant failure rates, making it unable to fulfil the rapidly increasing therapeutic demands. In this context, drug repurposing, identifying new therapeutic applications for existing medications with proven safety profiles, has emerged as a potential and cost-effective alternative to traditional drug discovery. Although numerous studies have explored the anticancer prospects of repurposed drugs, there exists a lack of systematic and cumulative knowledge regarding the varied therapeutic classes of interest for oncological purposes. This is critical as a deeper understanding of mechanisms, discovery methods, and translational challenges would significantly boost the clinical use of repurposed drugs. This review provides an overview of ongoing drug repurposing activity in anticancer therapy, targeting diverse therapeutic groups like cardiovascular, antibacterial, antiviral, anti-inflammatory, antidepressant, and antipsychotic drugs. It highlights approved drugs such as metformin, which acts on the AMPK/mTOR pathway to suppress cancer cell proliferation, thalidomide, which is approved for use in multiple myeloma because it has antiangiogenic and immunomodulatory effects, and propranolol, which inhibits β-adrenergic signaling, suppressing VEGF-induced angiogenesis in breast and ovarian cancer. Drugs such as statins, sertraline, and ribavirin target different pathways like HMG-CoA reductase, autophagy regulation, and eIF4E inhibition, respectively. Regulatory pathways like the FDA's 505(b)(2) process, orphan drug status, and approaches for overcoming intellectual property issues are discussed. Through the convergence of mechanistic insight and clinical and regulatory perspectives, drug repurposing is a pragmatic approach to expand oncologic therapeutic options and promote bench-to-bedside translation. It also addresses major issues within this context, including tumor heterogeneity, regulatory barriers, and translational gaps, restricting clinical acceptance of repurposed drugs. Through the examination of these aspects, the potential of drug repurposing as an innovative strategy in oncology is shown to offer efficient, cost-effective, and rapidly deployable therapy. These options can enhance patient outcomes and change the future of cancer treatment.