Drug Repurposing: New Uses for Old Drugs - PDF Version
There is an urgent need to improve therapeutic outcomes and long-term survival in many cancer types. But with the slow pace and high cost of cancer-drug discovery and the high clinical failure rates, progress is slow. An exciting alternative is the repurposing of approved or investigational drugs for common and rare diseases for off-label indications such as for anti-cancer treatment. This is appealing because approved drugs have known safety profiles and can be produced at significantly reduced cost and can yield faster clinical results than untested new drugs. Well known examples are sildenafil citrate (Viagra), which was originally prescribed for angina, and thalidomide, a sedative now used to treat multiple myeloma. Reduced cancer incidences are reported in large patient-cohort studies, which correlate to prescription medication for diabetes and heart failure. Examples include metformin, aspirin, and the cholesterol-lowering statins. During the past decade, preclinical studies have demonstrated enhanced antitumour activity in combination treatments for anti-diabetics (e.g metformin), anti-parasitics (e.g chloroquine), anti-microbials (atovaquone), anti-psychotics (e.g. imipramine, promethazine) and lipid-reducing drugs (e.g. statins, fibrates), among others. Repositioned (repurposed) drugs are applied increasingly in combination with chemotherapy and radiotherapy.
In this quarterly issue of the RB corner, PhD students and postdocs from the departments of Radiotherapy and Precision Medicine at Maastricht University highlight a selection of papers that show the potential of these compounds. These new uses for old drugs not only identify novel cancer vulnerabilities, but also create new biological understanding of the roles of on-target and off-target effects on cancer progression. While drug repurposing to enhance cancer treatment brings exciting opportunities and is economically beneficial, it is still in its infancy and clinical benefits remain uncertain. It is important to realise that new toxicities of these old drugs may manifest during use for their anti-cancer activity (off-target), and higher concentrations or treatment durations may be required to achieve therapeutic efficacy. Despite the urgency to identify new cost-effective anti-cancer medication, careful preclinical studies are required to reduce clinical attrition rates before these drugs progress into clinical pipelines. Because many of these drugs have generic versions and are off-patent, new ways to finance such clinical trials in public-private partnerships must be developed.
Further reading: Drug repurposing: progress, challenges, and recommendations. Nature Reviews Drug Discovery doi:10.1038/nrd.2018.168
Vitamin D analogues as adjuvant to improve radiotherapeutic effects
Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism
Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer
Salicylate enhances the response of prostate cancer to radiotherapy
Antidiabetic Biguanides Radiosensitize Hypoxic Colorectal Cancer Cells Through a Decrease in Oxygen Consumption
A Novel Mechanism of High Dose Radiation Sensitization by Metformin
HMG-CoA Reductase Inhibition Delays DNA Repair and Promotes Senescence After Tumor Irradiation
Dr Marc Vooijs, PhD
Professor and Chair of Department of Radiotherapy (MAASTRO)
GROW-School for Oncology
Maastricht University Medical Centre (MUMC+)