Repurposing statins for RDEB skin cancer

Researchers have confirmed that lovastatin effectively slows the growth of RDEB tumour cells in the laboratory, even showing signs of making them less likely to spread. They’ve found that not all tumour cells respond the same way and have identified a possible way to predict how well a tumour might respond to this statin treatment.

A researcher on this project was awarded “Best Oral Presentation” at The Austrian Society of Dermatology and Venereology Science Days 23-25 January 2025. 

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Lead researcher:

Dr Roland Zauner is involved in several projects with specific focus on bioinformatic analysis and interpretation of various -omics data. He established the current computational drug screening approach (Zauner et al 2022), which forms the foundation of this project.

Co-researchers:

A/Prof Verena Wally, group leader and deputy head of research at the EB House, has a long-standing interest in developing small molecule-based therapies that specifically target the biology of EB. She has a proven track-record in drug repurposing as well as several clinical studies conducted with EB patients.

Dr Christina Guttmann-Gruber is a group leader at the EB House Austria. She has extensive experience in working in the field of EB research with a special focus on EB tumor biology, wound healing and EB microbiome.

Dr Sonja Dorfer has been involved in the conceptualisation and establishment of the project.

“Our primary aim in this project is to investigate and evaluate the efficacy of statin-class drugs in slowing the growth and/or elimination of tumor cells. Our choice to prioritise repurposing already approved drugs over screening for new, patentable drugs is patient-centric and motivated by the urgent need for additional therapeutic options for the treatment of RDEB-tumors, as the use of existing drugs allows for an accelerated research process.”

– Dr Roland Zauner

Grant title: Investigating the potential of repurposing statins for the treatment of highly aggressive RDEB-tumors.

In addition to the already considerable burden on RDEB patients, one of the serious and life-threatening consequences is the high risk of developing a particularly aggressive form of skin cancer. Because currently there are very limited therapeutic options, surgical removal of affected tissue is often the only treatment option in fast progressing tumors. Tragically, the aggressive progression tumors often also require amputation (up to 42%, Tang et al 2021). Therefore, there is an urgent need to find new ways to treat RDEB tumors effectively and halt their progression. The fact that RDEB is a rare disease makes it challenging to develop new treatments by conventional means, as industrial research typically takes decades and costs hundreds of millions of pounds. Recent efforts to genetically fingerprint RDEB tumors allow us to use novel technological approaches to find new uses for existing drugs – a process known as “drug repurposing”. This presents an exciting opportunity for a faster, safer and cheaper approach to identify already approved drugs that can be effective in fighting cancer in RDEB patients. In our current project, we envision using statins – a class of drugs that has been known and used for decades to treat high cholesterol. Our work will identify the clinical utility of statins to stop tumor growth and provide fundamental data to encourage a clinical trial. Not only will RDEB patients ultimately benefit from this proof of concept study, but it will also provide further insights into specific patho-mechanisms RDEB tumors exploit and motivate further efforts within the research community.

The current lack of approved treatment options beyond surgical excision to target highly aggressive squamous cell carcinomas (SCC) occurring in patients with recessive dystrophic epidermolysis bullosa (RDEB) requires innovative schemes to drug development. In a novel approach using computational drug screening exploiting available gene expression data has revealed a potential anti-tumor effect of statin-class drugs. Given that statins are approved by regulatory authorities (EMA, FDA) for lowering cholesterol and in general well-tolerated, they offer an immediate, safe and inexpensive opportunity for repurposing. To provide a sound rationale for considering the reuse of statins as a treatment option for RDEB tumors, we propose a proof-of-concept study that will provide fundamental and pivotal preclinical data.

Recent developments in genetic profiling of tumors enable us to harness innovative technological methods to explore new applications for existing drugs, a process known as “drug repurposing.” This presents a promising opportunity for a rapid, safe, and cost-effective approach to identifying already-approved drugs that may be effective in treating cancer in EB patients. In our current project, we aim to investigate the use of statins—a class of drugs traditionally used since 1987 for managing high cholesterol. During recent decades, multiple studies focused on the cholesterol research and more recently on the anti-cancer effects of statins. Our research project is making significant strides in exploring whether statins can be repurposed as a new treatment for aggressive skin cancers in individuals with Recessive Dystrophic Epidermolysis Bullosa (RDEB). We’ve confirmed that lovastatin effectively slows the growth of RDEB tumor cells in lab settings, even showing signs of making them less likely to spread. This happens by blocking a specific cellular pathway. Importantly, we’ve found that not all tumor cells respond the same way, and we’ve identified a key marker, which might help us to predict how well a tumor might respond to statin treatment. This work is not only deepening our understanding of if and how statins could help to fight these challenging tumors but also helping us overcome hurdles to bring this promising new treatment closer to clinical trials. (From 2025 progress report.)