- Prof. Frank Rösl, Principal Investigator
- Prof. Edward Geissler, Co-Investigator
- PD Dr. Ingo Nindl, Co-Investigator
- Prof. Dr. Eggert Stockfleth, Clinical Collaborator
- Deutsches Krebsforschungszentrum, Heidelberg, Germany
- Reducing Skin Cancer in Organ-Transplanted Persons
The success of organ transplantation remains dependent on drugs that suppress the recipient’s immune system from destroying the foreign transplanted tissue. Unfortunately, cancer cells are not as likely to be destroyed in transplant recipients when their immune system is inhibited. In addition, it is thought that the conventional immunosuppressant cyclosporine may directly act to promote cancer development. Skin cancer is particularly common in transplant recipients, to the extent that half or more have had cutaneous lesions by 10-20 years post-transplantation. Presently, the course of action is to remove the lesion, but lesions can be numerous, tend to recur, and have an increased risk to be aggressive. Therefore, it is not only troublesome and costly to continually treat the lesions; they eventually pose a serious risk for malignant disease.
The present study aims to better understand factors that could be altered in these patients to reduce the risk of skin cancer. We are particularly interested in studying the potential role of cutaneous papilloma virus (PV) infections in skin cancer development, and the influence of different immunosuppressive drugs on this process. For this purpose we have a unique animal available, referred to as Mastomys natalensis (a mouse-rat intermediate). Like humans, these animals are latently-infected with PV and spontaneously develop skin cancer. Using this model, we predict that a newer-age class of immunosuppressants, referred to as mTOR inhibitors, will reduce PV-induced skin carcinogenesis, in contrast to conventional cyclosporine immunosuppression. We aim to show that mTOR inhibitors interfere with molecular pathways critical for PV-cell latency/replication, and for PV-induced tumor angiogenesis, thus reducing the risk of skin cancer. To support our theory, PV-infected skin lesions will also be studied in transplant recipients on either mTOR inhibitors, or cyclosporine. This study will form a scientific basis for potentially reducing the problem of post-transplant skin cancer.