HYPOTHESIS
There is an inflammation-dependent, context-specific effect of Inflammatory Skin Diseases (ISDs) on cancer development.
Background & Significance
Millions of people suffer from ISDs like psoriasis and their co-morbidities. However, the connection between psoriasis and cancer risk is far from being established. Depending on cancer type, psoriasis could be promoting cancer development or favouring immune-protection from tumor cells. We established in the past 10y several powerful GEMMs for acute and chronic inflammatory skin diseases to model human diseases30. Our data suggest that the skin acts like an endocrine organ keeping epithelial differentiation and inflammation under transcriptional control, e.g. by AP-1 (Fos/Jun) transcription factors31. We showed that the loss of JunB/AP-1 expression from epidermal/keratinocytes leads to a multi-organ disease affecting the skin, bones, kidneys, and the hematopoietic system. We have not yet investigated whether a particular inflammatory ‘state’ promotes or inhibits skin cancer.
Objectives
Provide trans-disciplinary training to an ESR through a project evaluating incidence and aggressiveness of non-melanoma skin cancer in the presence of inflammatory skin disease. ESR7 has to
determine spontaneous and chemically-induced skin tumor development in mice with a psoriasis-like disease or with an inducible IL-17-dependent inflammatory skin disease (above & unpublished data);
determine skin cancer risk in psoriasis patient-derived xenograft models (PDX) upon chemical carcinogenesis protocols;
identify mediators of inflammation associated with altered skin cancer rates;
validate the findings from GEMMs in human samples.
Enrolment in Doctoral degree(s):
- Medical University of Vienna