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How can cell mechanisms in RDEB Skin Cancer inform us about potential therapies?

Grant Title: Mechanisms of TGF-beta mediated tumour promotion in RDEB cSCC

Investigator: Professor Gareth Inman

Collaborators: Dr Peter Bailey, Dr Karen Blyth (Glasgow, Scotland, UK) and Dr. Andrew South (Thomas Jefferson University, Philadelphia, US).

Institution: Cancer Research UK Beatson Institute, University of Glasgow, Scotland, UK

Start Date: 02/01/2019 for 1 year

Grant amount:  £78,613.00 

Lay Summary 

About this research and why it is important: 

Recessive Dystrophic epidermolysis bullosa (RDEB) is an inherited disorder associated with chronic blistering, wounding and excessive scarring of the skin. A high proportion of RDEB patients develop a skin cancer called cutaneous squamous cell carcinoma (cSCC), which is often fatal. Cells within the body rely on specific signals for survival and growth. In cancer these signals are either lost or can be elevated to assist tumour growth and spread.

This research group and others have recently shown that a specific signalling system, involving a molecule called Transforming Growth Factor- beta (TGF-β), is elevated in the skin of people with RDEB related cSCC. Importantly this group has found that blocking active TGF-β signalling can inhibit (stop) cancer cell growth in 50% of RDEB samples tested. Interestingly, blocking the signaling pathway can also promote cancer cell growth in selected RDEB cSCC samples.

These observations indicate that it is critical to understand when and how TGF-β functions to promote or suppress cancer growth in RDEB to enable identification of patients that will benefit from inhibiting this signaling pathway. In this project the group plan to investigate how TGF-β promotes cancer growth and to achieve this, the group aims to develop biomarkers of TGFβ signalling using in-vitro and in-vivo state of the art biological assays, (procedures used to analyse the behaviour and activity of molecules);

Objective 1.

To understand the molecular characteristics (biomarkers) of how TGFβ behaves in RDEB skin cancer that will inform the use of an anti - TGFβ signalling therapy. 

Objective 2.

Understand the mechanism of how TGFβ signalling can lead to cancer migration, invasion and tumour growth and identify targets for therapeutics (e.g. a protein or molecule that can be modified using a drug or treatment to target cancer cells). 

In Summary

This research will provide the basis for further understanding of TGFβ signaling in RDEB and could identify new targets for future drug development to treat squamous cancers. These therapies are in clinical trials in other cancers or are in pre-clinical development already. The study will also inform on avenues of novel therapeutic development.

For more information about the research in to TGF-β signaling in RDEB cSCC by Professor Gareth Inman that contributed to this new research, please click here -https://www.debra.org.uk/uk-funded-projects/inman-tgf-i 

The research for TGF-β signalling in RDEB cSCC project will be completed by 2019.

 

Investigator Biography

Professor 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. By understanding TGFβ’s role as both a cancer promoter and a cancer inhibitor Professor Inman hopes to develop strategies for future cancer therapeutics.