PhD: fighting RDEB skin cancer

Due 2026

Research leader:

Professor Gareth Inman is Director of Research Strategy at the CRUK Scotland Institute, Research theme lead for the CRUK Scotland Centre and Director of Research and Professor of Cell Signalling in the School of Cancer Sciences in the University of Glasgow.

Co researcher:

Professor Mellerio is a leading clinician in the EB field at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust. She holds an Honorary Chair of Paediatric Dermatology at King’s College London and leads one of the two national adult epidermolysis bullosa services.

“These studies will pave the way for rapid deployment of drug therapies already approved for use, in clinical trials for RDEB cSCC sufferers.”

Title: Integrated pharmacological and genetic identification of therapeutic targets for RDEB Squamous Cell Carcinoma

RDEB patients frequently develop early onset multiple aggressive skin tumours (cSCC). In nearly all cases they have lethal consequences. A detailed understanding of RDEB cSCC remains disappointingly elusive and there are no effective treatments or approved targeted therapies. There is an urgent need to rapidly identify therapeutics for RDEB cSCC and to rigorously evaluate them in stringent relevant pre-clinical models prior to testing in patients in clinical trials. Investigation of the molecular basis of RDEB cSCC development and progression will continue to inform novel target identification. The process from target identification to drug development, preclinical testing, dose, scheduling, safety and toxicity testing and then clinical implementation can take many years. It can also be prohibitively costly, particularly in the rare disease setting where the patient population is relatively small.

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. Integration of our findings from a drug re-purposing screen of over 3,000 drugs already approved for use in patients with other disease conditions with analysis of gene expression data from RDEB patient samples and cSCC cell lines has revealed several drugs and their targets as potential therapeutic vulnerabilities for treatment of these devastating cancers. We will validate our findings in our rigorous pre-clinical models, develop biomarkers for their use and seek to present a strong case for the testing of 2 or more drugs in clinical trials in RDEB cSCC patients.

Recessive Dystrophic Epidermis Bullosa (RDEB) is caused by inherited mutations in the COL7A1 gene that encodes type VII collagen (C7), the principal component of anchoring fibrils that are required for the structural integrity of the epidermal-junction in the skin. RDEB patients suffer from severe skin fragility, persistent skin blistering and wounding. They have an exceptionally high risk of developing early-onset, aggressive and ultimately lethal cutaneous squamous cell carcinoma (cSCC). There is currently an incomplete understanding of the pathogenesis of RDEB cSCC and no currently clinically approved targeted treatment therapies.

Integration of our findings from a drug re-purposing screen of over 3,000 drugs already approved for use in patients with other disease conditions with analysis of gene expression data from RDEB patient samples and cSCC cell lines has revealed several drugs and their targets as potential therapeutic targets for treatment of these devastating cancers. Here we will validate these findings and develop biomarkers for their use in patients and further explore the possibility of inducing cancer cell death with a novel class of death inducers called BH3 mimetics. We will then go on to identify new potential drug targets genome wide.

These studies will pave the way for rapid deployment of drug therapies already approved for use in clinical trials for RDEB cSCC sufferers.

Due 2026