Over 3000 approved drugs will be screened to identify those that kill skin cancer cells and could be repurposed to treat the aggressive form of skin cancer which frequently affects people with RDEB.

Prof Gareth Inman works at the University of Glasgow, UK, on skin cancer in RDEB. In this project, he 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.

  

My greatest fear for my skin is cutaneous squamous cell carcinoma. Let's end this please!

(Comment from member review)

 

Contents:

• Project summary (top of page)
• About our funding
• Latest progress summary
• About our researchers
• Why this research is important
• Researcher’s abstract
• Researcher’s progress update

 

About our funding:

Research leader	Prof Gareth Inman
Institution	Cancer Research UK Beatson Institute, University of Glasgow, Scotland, UK
Type of EB	RDEB
Patient involvement	None - patient cells are grown in the laboratory
Funding amount	£96,891.52 (co-funded with DEBRA Ireland)
Project length	18 months
Start date	TBC 2023
DEBRA internal ID	GR000012

 

Latest progress summary:

Due 2024.

 

About our researchers:

Research Leader: Prof Gareth Inman is the Director of Research Strategy at The CRUK Beatson Institute for Cancer Research and Professor of Cell Signalling in the Institute of Cancer Sciences, University of Glasgow, Scotland. His primary interests are to understand the role that members of the Transforming Growth Factor Beta (TGFβ) family play in cancer development and progression. His studies are focused on squamous cell carcinomas of the skin, head and neck and pancreas and now involve these cancers arising in patients living with Recessive Dystrophic Epidermolysis Bullosa.

Co-researcher: Prof Karen Blyth, senior staff scientist at CRUK Beatson Institute.

Collaborators: Prof Owen Sansom, Prof Crispin Miller, Dr Leo Carlin, Dr Lynn McGarry (all at CRUK Beatson Institute); Dr Andrew South (Thomas Jefferson University, Philadelphia) and Prof Irene Leigh (Queen Mary’s University, London, UK).

  
Why this research is important:

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.

Prof Gareth Inman

 

Researcher’s abstract:

Grant Title: Drug repurposing for the treatment of RDEB squamous cell carcinoma.

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 and have an exceptionally high risk of developing early-onset, aggressive and ultimately lethal cutaneous squamous cell carcinoma (cSCC). RDEB cSCC develops in a permissive environment of chronic inflammation, wound healing and fibrosis facilitated in part by cancer associated fibroblasts (CAFs). There is currently an incomplete understanding of the pathogenesis of RDEB cSCC and no currently clinically approved targeted treatment therapies.

Here we will undertake a drug re-purposing screen of over 3,000 drugs already approved for use in patients with other disease conditions. We will develop and refine a stringent step-wise pre-clinical pipeline designed to assess the efficacy of drugs for inhibiting RDEB cSCC tumour cell survival both in-vitro and in-vivo; important indicators of therapeutic use. We will reveal the importance of CAFs in tumourigenesis and drug response and we will identify 2 drugs which show efficacy all the way through our pipeline.

This process will circumvent the prohibitively time consuming and costly process of drug development and safety testing and will provide compelling evidence for the rapid and safe deployment of these 2 drugs in patients in clinical trials for RDEB cSCC therapy.

 
Researcher’s update:

Due 2024.

 

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Image credit: 96-well plate, by Jaime Neto. Licensed under the Creative Commons Attribution-Share Alike 4.0 International license.