Existing drugs can be repurposed into cost-effective treatments for different illnesses, but there are barriers to drug repurposing. Photo credit: Julia Koblitz via Unsplash
Introduction
Nobel Prize winner James Black once remarked, ‘The most fruitful basis for the discovery of a new drug is to start with an old drug’. He is often spectacularly right. Sildenafil began as a potential drug for chest pain before an unexpected side effect sent it down a rather different path. Today, sildenafil is better known as Viagra. Finding a surprising new use for an old drug is one thing; proving that it works, especially against cancer, can be much harder.
New uses may emerge when researchers discover that an existing drug affects more biological pathways than originally investigated, doctors make unexpected clinical observations, or advances in research change our understanding of disease biology. Repurposing has already transformed some areas of oncology. Arsenic trioxide, once used for skin conditions, and all-trans retinoic acid, once used to treat acne, are now central to the treatment of a type of blood cancer known as acute promyelocytic leukaemia.
Why start with an old drug?
Starting with an existing drug means that researchers are not starting from scratch. Previous laboratory studies, clinical trials, and patient data may already have established how the drug behaves in the body, how well patients tolerate it, and which side effects to expect. Although further testing is needed to establish its safety and effectiveness for a new use, this existing knowledge can reduce development time and costs. However, a 2025 study found that repurposed drugs had lower overall clinical trial success rates than drug development programmes generally in recent years, despite tending to perform better in early-stage trials.
Drug repurposing provides researchers with access to a vast library of compounds whose biological effects in humans are at least partially characterised. Some interact unexpectedly with cancer-relevant pathways, potentially revealing therapeutic opportunities that might not emerge from designing a new drug against one predetermined target.
…drug repurposing may expand the arsenal of treatments available.
Cancer is not a single, static target. Even within a single tumour, groups of cancer cells can differ from one another. Treatment may kill some cells, while others become resistant, so they survive and multiply, allowing the cancer to return. By identifying drugs that act on different biological pathways, drug repurposing may expand the arsenal of treatments available, without requiring every weapon to be designed anew.
A question of access
The potential benefits extend beyond the laboratory. The high cost of cancer treatment can in itself cause harm to patients, a phenomenon termed “financial toxicity”. High medical costs can contribute to delays in and discontinuation of treatment, reducing quality of life. One study found that colorectal and prostate cancer patients who declared bankruptcy had more than twice the risk of death of those who did not.
Affordability is only one barrier to treatment; where new drugs become available is another. Since the mid-1990s, death rates due to cancer have declined in most high-income countries, but they have increased in many low-income countries. Inequality is also reflected in access to new treatments. Of 568 cancer drugs first launched globally between 1990 and 2022, almost half were launched in only one country, and the average delay before a second-country launch was 18 months. In 2022, high-income countries launched an average of 8.7 new cancer drugs per country, compared with 0.3 in lower-middle-income countries and none in low-income countries. Effective treatments based on inexpensive, already manufactured drugs could offer not only a shortcut through drug development, but also an opportunity to widen access.
In 2022, high-income countries launched an average of 8.7 new cancer drugs per country, compared with 0.3 in lower-middle-income countries and none in low-income countries.
From fungus fighter to cancer treatment?
One source of possible repurposed cancer treatments is perhaps unexpected: antifungal drugs. Fungi and humans share some basic cellular machinery, meaning that drugs developed to interfere with fungal cells can sometimes have unexpected effects on human cells too. Some antifungal drugs have been found to interfere with processes that cancer cells depend on, making them promising candidates for drug repurposing.
Itraconazole, normally used to treat fungal infections, is one example. Researchers have found that it can interfere with several processes involved in cancer growth and drug resistance. It may restrict the blood supply that growing tumours need and disrupt signals that encourage cancer cells to grow. Laboratory studies have even suggested that treatments including itraconazole can make some chemotherapy-resistant cancer cells sensitive to treatment again. These findings suggest that itraconazole may ultimately be useful in combination with other drugs for specific patient groups.
Promise, but proof?
A plausible biological explanation is very different from showing that a drug actually benefits patients. In 2013, a clinical trial involving 23 people with advanced lung cancer tested whether adding itraconazole to the chemotherapy drug pemetrexed improved patient outcomes. Patients receiving itraconazole and pemetrexed (n=15) survived for a median of 32 months, compared with eight months for those receiving pemetrexed alone (n=8). The trial was originally planned to recruit 112 people, but was ended early because pemetrexed was increasingly being used as a first-line treatment, leaving fewer patients eligible to participate. The survival difference is striking, but with only 23 participants, the trial could not provide conclusive evidence that itraconazole improved survival.
A plausible biological explanation is very different from showing that a drug actually benefits patients.
Several clinical challenges remain. Itraconazole is absorbed inconsistently, can cause side effects at therapeutic doses and can have harmful interactions with other drugs. Researchers also lack reliable ways to identify which cancer patients are most likely to benefit. Itraconazole captures both the promise and uncertainty of drug repurposing, but without further work, these encouraging laboratory results and small trials do not establish that it is an effective cancer drug.
The drug repurposing catch-22
Once a drug’s patent expires, other manufacturers can sell generic versions. That creates a problem for drug repurposing. Early laboratory research may attract public or charitable funding, but it can cost millions of dollars to undertake the large trials needed to prove that a drug can safely and effectively be used in clinics. Universities and charities rarely have the resources to take a drug through the full clinical trial process.
This creates a catch-22: without investment in large clinical trials, promising laboratory findings and early trials may never yield sufficient evidence to demonstrate that a repurposed drug benefits patients. Yet without strong evidence, gaining regulatory approval and attracting further investment is difficult, leaving a drug suspended between scientific promise and clinical use.
A lack of investment does not necessarily mean that an effective cancer drug is being overlooked. Itraconazole provides a useful example: promising mechanisms may fail to translate into meaningful benefits for patients for clinical reasons.
Thus, the challenge is not simply persuading pharmaceutical companies to test more inexpensive drugs; it is to identify candidates with enough evidence to justify that investment, and to distinguish between drugs held back by weak financial incentives and those that do not warrant further development.
If pharmaceutical companies do not pay, who does?
The NHS established the Medicines Repurposing Programme in 2021 to support the development and implementation of new uses for existing drugs. By bringing healthcare organisations, researchers, and other stakeholders together, the programme aimed to overcome some of the coordination and regulatory barriers that individual researchers face when translating evidence into routine NHS practice.
Yet the programme itself illustrates the difficulty of the problem. There were fewer opportunities for drug repurposing than originally anticipated, partially because few candidate drugs had evidence strong enough to support a variation to their licence. The programme was suspended in April 2025. The programme’s experience suggests public coordination can address some commercial and organisational barriers, but it cannot substitute for robust clinical evidence.
The Repurposing Drugs in Oncology (ReDO) project takes a broader, international approach. It searches published research for existing non-cancer drugs with evidence of anticancer activity and compiles that evidence in an open database. Researchers identified 268 existing drugs, 84% of which were already off patent and 66% of which had been or were being tested in clinical trials. By bringing together scattered evidence, ReDO can help researchers identify which inexpensive drugs are most promising for further investigation. Still, promising drug candidates require large clinical trials to establish efficacy for the new use.
Proposed solutions include greater sharing of pharmaceutical data, new ways for researchers and manufacturers to share the financial rewards of drug repurposing, and closer collaboration between governments, academics, charities, patient groups and industry. No single model removes the fundamental problem. Someone must decide which candidates deserve definitive testing, and someone has to pay for it.
Someone must decide which candidates deserve definitive testing, and someone has to pay for it.
Conclusion
James Black’s observation still rings true. Sometimes the ingredients of tomorrow’s treatments are already sitting on today’s pharmacy shelves. Drug repurposing can build onyears of existing knowledge about a drug, potentially reducing some of the costs and risks associated with developing a treatment, but also the profit, especially in the case of off-patent drugs. Yet scientific promise does not guarantee clinical success, and even inexpensive drugs require substantial investment to prove they work.
This creates a paradox. Repurposed drugs could offer more affordable treatments, but limited opportunities to recover development costs can discourage the investment needed to establish their effectiveness. Decisions about which drugs deserve further testing should be guided by scientific evidence and public-health need, not solely by the prospect of profit. Without that investment, promising treatments may never be properly evaluated, and old drugs may just remain old drugs.
Edited by Andy Garnier, Veronika Ilinčeva and Iulia Kis
