Drug Repurposing Unlocks Novel Therapeutic Approaches

1 Developing a new drug from scratch is a long and expensive process. It takes more than a decade of effort and more than $2 billion to take a drug from target identification to market product. Add to this the risk that the majority of candidates fail before they ever reach patients, and it’s no wonder drug repurposing is becoming an increasingly appealing shortcut. Also known as drug repositioning, this strategy involves identifying new therapeutic uses for drugs that have already been approved, or at least extensively tested, for a different indication. Because repurposed drugs have established safety profiles and known pharmacological properties, they can leapfrog many of the early-stage hurdles that slow conventional drug development. The COVID-19 pandemic brought repurposing sharply into focus, as researchers worldwide rapidly screened existing medicines for activity against SARS-CoV-2. But the strategy is far from new. This listicle explores the strategies and real-world examples that illustrate why drug repurposing is becoming an increasingly important tool in the current pharmaceutical toolkit. 1. Sildenafil and the art of happy accidents Like so many great discoveries, drug repurposing often begins with unexpected observations. In the case of sildenafil, known more commonly as Viagra®, the compound was originally investigated as a treatment for hypertension and angina. However, during clinical trials, participants reported one noticeable side effect: improved erectile function. Rather than dismissing this observation, researchers pivoted their focus, and in 1998, the compound was approved by the US Food and Drug Administration (FDA) for erectile dysfunction. This shift highlights that a drug's mechanism of action may have therapeutic relevance beyond its original target. Along similar lines, it is now possible to mine clinical trial adverse event data and electronic health records to identify side effects that could unlock new avenues for repurposing. Drug Repurposing Unlocks Novel Therapeutic Approaches Giving existing medicines a second life can save lives. Steven Gibney, PhD Listicle DRUG REPURPOSING UNLOCKS NOVEL THERAPEUTIC APPROACHES 2 Listicle 2. Thalidomide and revisiting abandoned medicines Originally marketed in the late 1950s as a sedative and treatment for morning sickness, the drug thalidomide was infamously withdrawn after its administration was linked to severe birth defects in thousands of children worldwide. For decades, thalidomide became synonymous with pharmaceutical failure. Rather than being lost to the annals of pharmaceutical history, researchers discovered that thalidomide also possessed potent immunomodulatory and anti-angiogenic properties. These mechanisms proved relevant to a range of diseases characterized by abnormal immune activity and blood vessel growth. The drug was subsequently approved for erythema nodosum leprosum, a complication of leprosy, and later became an important treatment for multiple myeloma. Thalidomide demonstrates that a failed or abandoned medicine may still hold therapeutic value when viewed through a different biological lens. This approach is becoming increasingly effective as advances in molecular profiling enable researchers to reassess shelved compounds and identify opportunities that may have been impossible to recognize when those drugs were first developed. 3. Dexamethasone and COVID-19 The COVID-19 pandemic provided one of the largest real-world demonstrations of drug repurposing. In the midst of a global health crisis, researchers rapidly screened existing medicines for potential activity against SARS-CoV-2 to identify treatments that could reach patients more quickly than newly developed drugs. One of the most notable successes was dexamethasone, a corticosteroid that had been used for decades to treat inflammatory conditions. Results from the RECOVERY trial showed that the drug reduced mortality in hospitalized COVID-19 patients requiring oxygen or mechanical ventilation, making it one of the first therapies shown to improve survival during the pandemic. The success of dexamethasone highlighted the strengths and limitations of repurposing. Many other candidates that appeared promising in laboratory or computational studies ultimately failed in clinical trials. For example, the antimalarial drug hydroxychloroquine generated interest during the early stages of the pandemic after laboratory studies suggested it might inhibit SARS-CoV-2. However, large randomized clinical trials found no meaningful benefit for hospitalized patients, illustrating that promising preclinical or computational signals must still be validated through clinical testing. The ability to rapidly evaluate existing drugs demonstrates how established safety data, combined with large-scale clinical research infrastructure, can accelerate the delivery of effective treatments during public health emergencies. 4. Genomics precision repurposing Advances in genomics now make it possible to match existing drugs to patient subgroups based on their molecular or genetic profile, rather than clinical diagnosis alone. One example is imatinib (Gleevec®), which was developed to treat chronic myeloid leukemia (CML) and targeted the BCR-ABL fusion protein. Subsequent research identified the same molecular target in other cancers, leading to imatinib's approval for gastrointestinal stromal tumors and several other malignancies that had previously been diagnosed on clinical grounds alone, but which share a targetable genetic driver with CML. DRUG REPURPOSING UNLOCKS NOVEL THERAPEUTIC APPROACHES 3 Listicle This approach is becoming more common as initiatives such as the UK Biobank and the NIH's All of Us program generate large datasets that link genetic variants to disease outcomes and drug responses. Mining these resources for repurposing is an active and rapidly growing area of research, offering hope for patients of rare diseases that may lack dedicated drug development programs. For example, genomic insights into the dysregulated mTOR pathway helped establish the mTOR inhibitor everolimus as a treatment for tuberous sclerosis complex. 5. AI, network biology, and the search for hidden connections Identifying new uses for existing medicines has traditionally relied on clinical observations and painstaking laboratory research. Today, advances in computational biology and AI are transforming the process into a data-driven search problem. One powerful approach is network medicine, which maps relationships between genes, proteins, pathways, and diseases. By overlaying a drug's known molecular targets onto these biological networks, researchers can identify unexpected connections that suggest new therapeutic applications. Such analyses have generated repurposing candidates across conditions ranging from neurodegenerative diseases to genetic disorders. Machine learning adds another layer of predictive power. Models trained on genomics, proteomics, electronic health records, and published literature can rapidly evaluate vast numbers of drug–disease combinations. Although experimental and clinical validation remain essential, these technologies are dramatically reducing the time and cost required to identify promising repurposing opportunities. The future of drug repurposing Drug repurposing is increasingly shifting from opportunistic discovery to a systematic component of pharmaceutical innovation. Regulatory agencies, including the FDA and European Medicines Agency, have established pathways that can help accelerate the development of medicines with existing safety data, while academic–industry partnerships are expanding access to compound libraries and clinical datasets. Challenges remain, particularly around intellectual property, commercial incentives, and the need for robust clinical validation. However, drug repurposing could be one way to turn decades of accumulated pharmacological knowledge into a searchable resource for therapeutic innovation. About the author: Dr. Steven Gibney has a BSc in pharmacology and a master's in bioscience from the University of Leeds, as well as a PhD in pharmacy from the University of Nottingham. After finishing his PhD, he spent two years working at an agency as a medical writer. Wanting to further develop his communication skills, he joined Technology Networks as a science writer in 2023..