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Validation of Ruxolitinib, a FDA-approved pharmacological inhibitor of JAK 1/2, as a therapeutic agent for dermal fibrosis and tumour invasion in RDEB (Gaggioli 2)

Project lead Dr Cedric Gaggioli
Organisation IRCAN, Nice, FRANCE
Partner organizations & collaborators Gaggioli, RDEB, IRCAN,
Project budget EUR 230,000.00
Start date / Duration 01. Oct 2013 / 40 months
Funder(s) / Co-Funder(s) DEBRA UK, EB MSAP/EBEP Recommended
Research area Skin cancer & fibrosis

Project details

Short lay summary

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is associated with skin blistering, soft tissue scarring and mitten deformities (where the skin encases the fingers and toes causing a mitten-like appearance of the hands or feet). The skin blistering is due to a lack of a skin protein, called collagen VII, which causes separation of the epidermis (outer layer of the skin) from the underlying dermis and the scarring is due to abnormal wound healing and over production of fibrous tissue. These abnormal skin reactions also frequently give rise to a kind of skin cancer called squamous cell carcinoma (SCC).

It has been found that in the skin of people with RDEB and also the skin of a mouse model of RDEB, there are inflammation-associated molecules in the area of blistering. Inflammation is known to be associated with the development of cancer, so these molecules might be contributing to the onset of SCC.

Important agents, called cytokines, are produced during inflammation. They have been shown to affect normal skin cells (fibroblasts) and induce them to become Carcinoma Associated Fibroblasts (CAF). These cells are involved in altering the structure of skin tissue (remodelling) and in this situation promoting the development of cancer. CAFs may play a part in SCC formation in RDEB.

Messages between the cytokines cause the conversion to CAFs. It is hoped that if these messages can be interrupted or stopped then it is possible that the development of cancer can be halted. A specific molecule, Janus kinase (JAK) in this messaging pathway has been identified. JAK can be blocked by a drug, Ruxolitinib that has already been approved by the Food and Drug Administration (FDA) in the US, for another condition.

In trying to reproduce what happens in people in the laboratory, it has been shown that fibroblasts treated with cytokines become CAFs, but their deleterious actions can be prevented by Ruxolitinib. This research group therefore want to look at whether Ruxolitinib can be a useful therapeutic agent for RDEB patients suffering from local inflammation and fibrosis associated with abnormal wound healing and in the long-term, prevents the development of aggressive SCC.


Strategic relevance

“This DEBRA funded research has enabled us to bring forward the scientific investigations that could lead to the development of an alternative therapeutic strategy for treating EB cancer.”

More on DEBRA UK's website.


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