Repurposing non-cancer drugs for breast cancer? An emerging opportunity.
Breast cancer (BC), the main cause of cancer death in women worldwide is a very important model to evaluate new treatment strategies. While new treatment modalities, like biologic agents, targeted immunotherapies, have given important results and offer promise for the future, these interventions will likely impose severe financial strains on health systems in high income countries and remain unaffordable for many low- and middleincome countries. Drug repurposing is an alternative development pathway that seeks to reuse existing medications, including non-cancer medications, as the source of new treatment options. Repurposing benefits from existing data on safety, tolerability, dosages and clinical experiences gained in the primary indications of these drugs.
Materials and Methods
The Repurposing Drugs in Oncology project, an international non-profit collaboration, has identified over 200 existing noncancer medications with potential utility in oncology. Well-known examples include beta-blockers, statins, metformin, angiotensin receptor blockers and aspirin but many more agents from multiple disease areas are supported by scientific evidence. About 75% of them are generic and 30% are included in the WHO list of Essential Medicines. In contrast to newly developed medicines, many repurposing candidates are affordable globally.
In the BC context several targets have been considered and specific repurposed medicines have been or are being tested in clinical trials alone or in combination with standard treatments, more particularly in three distinct clinical settings. Firstly, as pre- or peri-operative therapies to identify potential biomarkers, to improve pathologic responses and to improve longterm surgical outcomes through reduction in locoregional and distant recurrence rates. Secondly, in association with adjuvant treatment to improve the efficacy (disease free survival) of current treatments. Thirdly, in recurrent-metastatic disease to improve the clinical benefit and/or other outcomes. Clinical trials are in progress in all BC subtypes including rare forms such as inflammatory BC. International multi-arm, multi-stage collaborative clinical trials seem to be an ideal platform for developing such novel BC interventions.
Drug repurposing and innovative trial designs offer the potential to address some unmet needs in BC and its subtypes. Serendipitous findings by astute clinicians, retrospective analysis of clinical records, sharing data from clinical trials, creation of data warehouse for sharing the data from clinical research across studies, investigator-initiated clinical trials (IIT), and Academia/industry-sponsored clinical trials (A-IST) are necessary to increase the success rate of drug repurposing also in BC.