Epidermolysis bullosa (EB) is a heritable skin disease characterized by marked fragility of
epithelialized tissue with blistering in skin and mucous membranes following the slightest
mechanical trauma. Eighty percent of all patients suffering from recessive dystrophic EB
(RDEB), a subtype originating from mutations in the COL7A1 gene, develop squamous cell
carcinoma (SCC). In RDEB patients SCC presents early (most patients are in their 20s or 30s)
and shows a highly aggressive metastatic course which often leads to premature death at this
young age.
In light of scarce data on the efficacy and safety of systemic treatment regimens for
advanced SCC, the investigators propose to perform a small, "first in EB " trial of an
experimental drug called rigosertib for the treatment of EB cancer. The trial will be
conducted in two study centres, in London and Salzburg, and will last approximately 2.5 years
with each patient recruited being in the study for 1 year. The drug is a polo-like kinase
inhibitor interfering with different molecular pathways that are essential for cancer cell
growth. Rigosertib was developed by Onconova Therapeutics and is currently tested in several
clinical trials for a number of other cancers including myelodysplastic syndrome (a cancer of
the blood). The investigators have identified that rigosertib most selectively kills EB
cancer cells in vitro while leaving normal EB skin cells unaffected. This project will
evaluate whether rigosertib is capable of inducing an anti-cancer response in EB patients and
whether the drug is well-tolerated. Mechanisms of molecular targeting of squamous cancer
cells by rigosertib will further be investigated in EB patients, also aiming at the
identification of biomarkers that may allow the predictive identification of best responders.