None of us want to imagine ourselves or our loved ones developing cancer. Unfortunately patients with recessive dystrophic epidermolysis bullosa (RDEB) can be at risk of developing a skin cancer called cutaneous squamous cell carcinoma. This is a non-melanoma skin cancer with a lower likelihood of spreading to other parts of the body than melanoma. 

There is hope though.

This World Cancer Day (February 4), we’re highlighting the research projects we fund to understand more about the progression of cancer in EB, and to investigate opportunities for future drug development to treat skin cancer.  

 

DEB cancer and mouth wound healing, Queen Mary University, London 

This project is led by Dr Inês Sequeira at Queen Mary University, London, and aims to understand scarless healing and cancer resistance in DEB.  

Wounds in the mouth should heal quickly, but this is not the case in DEB. However, even people with DEB rarely get cancers occurring inside their mouths.  

By comparing cells lining the mouth in people with and without DEB and by comparing mouth lining to skin, this project hopes to identify ways to help EB wounds heal and prevent them from progressing to non-healing chronic wounds or cancer. 

There is an acute need to translate our understanding of RDEB biology into an ability to detect, predict, or prevent the degeneration of an acute wound into a non-healing fibrotic site and into a tumour.

Dr Inês Sequeira

  

Read more about this project

  

Repurposing statins for RDEB skin cancer, EB House, Austria 

Led by Dr Roland Zauner at the EB House, Austria, this project aims to provide evidence for repurposing statins as a treatment for RDEB skin cancer before a trial can be carried out in people.  

Preliminary screening and experiments suggested that statins could work and this research aims to show that they do kill EB cancer cells in the laboratory, how they do this, and to see if this translates into actually eliminating tumours. 

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

  

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Read Dr Ronald Zauner's blog

  

Screening drugs to target RDEB cancer, University of Glasgow 

Led by Professor Gareth Inman at the University of Glasgow, this project will apply over 3000 approved drugs to cells grown in his laboratory to identify those that kill cancer cells without harming non-cancer cells. Those that pass the screening will be subject to further testing to generate evidence to support their use in future drug repurposing clinical trials. 

The potential of drug re-purposing of drugs already clinically approved for safe use in patients with established dose and scheduling regimens holds exciting potential for EB patients. Here we will undertake an unbiased drug re-purposing screen of over 3,000 FDA approved drugs... At the completion of these studies we will have identified and taken 2 drugs all the way through our pipeline which will provide compelling evidence for their rapid deployment in clinical trials in RDEB patients for treatment of the ultimately lethal cancer complication of this devastating disease.

Professor Gareth Inman

 

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RDEB skin cancer, University of Glasgow 

Also led by Professor Gareth Inman, this research aims to increase understanding of the behaviour of a particular molecule and identify new opportunities for future drug development to treat skin cancer. 

A substance called transforming growth factor beta (TGF-β) is found at higher levels in the skin of RDEB patients with skin cancer. Deactivating TGF-β can stop cancer cell growth in some samples but increase it in others. Before therapies that inactivate TGF-β can be developed, this project will help to understand more clearly how it is involved in the growth and movement of cancer cells. 

RDEB patients will ultimately benefit from this research, not only in the context of cancer but also the proposal will potentially inform on how TGFβ signalling contributes to the gradual deterioration of overall dermal architecture. TGFβ therapies are in clinical trial and this proposal will determine when they will have clinical utility for RDEB patients. SCC arising in other forms of EB may also benefit from these studies.

Professor Gareth Inman

  

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KEB and skin cancer, Edinburgh, UK 

Prof Valerie Brunton works in Edinburgh, UK, on a rare type of epidermolysis bullosa (EB) called Kindler EB. This is caused by genetic changes that mean the Kindlin-1 protein doesn’t work properly. Patients suffering with this form of EB have thin skin that blisters and sunburns easily and an increased risk of skin cancer (squamous cell carcinoma). This work studies how the growth and spread of skin cancer is related to Kindlin-1 protein. 

Our research has uncovered important changes in the tumour microenvironment (the normal cells and molecules that surround and support the growth of tumour cells), that are controlled by Kindlin-1. By studying these changes, we hope to gain a better understanding of how we can prevent the development and progression of skin cancer in patients with Kindler syndrome.

Prof Valerie Brunton

  

Read more about this project

Read Dr Giovana Carrasco's blog