Preclinical assessment of PLK 1 inhibitors for the treatment of recessive dystrophic epidermolysis bullosa associated with squamous cell carcinoma (South 2)Completed
|Dr Andrew South
|University of Dundee, Dundee, UK
|Start date / Duration
|01. Nov 2013 / 24 months
|Funder(s) / Co-Funder(s)
|DEBRA UK, MSAP/EBEP Recommended
|Skin cancer & fibrosis
Short lay summary
People with Recessive Dystrophic EB (RDEB) often develop a type of skin cancer called squamous cell carcinoma (SCC), for reasons we do not fully understand. This cancer is life-threatening so poses a serious problem for RDEB patients. An important driver, causing cells to multiply, in several types of cancer is a molecule called Polo-Like Kinase 1 (PLK1). It acts like the car accelerator to make the tumour grow faster. This research group, working with previous DEBRA funding, have shown that PLK1 is indeed acting as a driver in SCC in RDEB patients and that inhibiting the action of PLK1 kills SCC keratinocytes (the most common cell type in the outermost layer of the skin). This inhibition can be regarded as taking a foot off the accelerator and pressing the brake in the car! Importantly, it does this without affecting normal skin cells. Many compounds are capable of inhibiting PLK1 in the laboratory under experimental conditions. The next challenge is to find one or more that are effective, yet safe to use in patients and act without detrimental side effects. As part of this challenge this project aimed to screen a panel of eight available PLK1 inhibitors to find the one(s) that may be effective in SCC cells from RDEB patients. This was done firstly in the test tube and then in a laboratory model.
What is important about this research?
The study identified three potentially useful compounds that kill cancer cells from this piece of research. One was not sufficiently specific for PLK1, but the research group hope to further develop the other two compounds to bring them towards clinical use for the treatment of RDEB SCC in the years to come.