PhD Conferral drs. Tjinta Brinkhuizen
Supervisors: prof.dr. M.A.M. van Steensel; prof.dr. M. Steijlen
co-supervisor: dr. K. Mosterd
“Basal Cell Carcinoma; Epigenetics and new treatment modalities. Out of the Box”
Keywords: basal cell carcinoma, genetics, epigenetics, non-invasive treatment
In the Netherlands, one in five people will develop basal cell carcinoma, the most common type of (skin)cancer. Surgical removal is the standard treatment for all variants of basal cell carcinoma. Although non-invasive treatments are available for superficial basal cell carcinomas, these are less effective compared to surgery. By analysing the whole genome, this dissertation demonstrates for the first time that in addition to genetic changes in basal cell carcinomas which were already known, epigenetic changes seem to play an important role as well. Epigenetic changes found in basal cell carcinomas lead to the activation of the immune system. These findings were supported by a study conducted in 124 patients. Treatment with diclofenac 3% gel (a well-known anti-inflammatory drug and painkiller) was shown to be effective by specifically inhibiting signalling pathways active in basal cell carcinomas, among other things. After applying diclofenac 3% gel for eight weeks, more than two-thirds of patients with superficial basal cell carcinoma were tumour-free. This is a first step towards more effective and specific non-invasive treatments. As a result of the involvement of several signalling pathways in basal cell carcinomas, the future lies in combination therapies.
This research project was partly funded by the Dutch Cancer Society (DCS)