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A computer-based screening method to identify drugs against aggressive skin tumors in RDEB

New scientific publication by working group from Dr. Wally

UV light is the greatest risk factor for the development of squamous cell carcinoma (SCC) of the skin. If this skin cancer arises in otherwise healthy individuals, it is well treatable. In contrast, RDEB patients who lack the collagen 7 protein frequently develop particularly aggressive SCCs, irrespective of UV exposure. The underlying mechanisms are not yet fully understood, and consequently the treatment options are poor. Similar to RDEB patients, also organ transplant recipients (OTRs) are at high risk for developing aggressive SCC, which is associated with long-term immunosuppression. Although the preconditions and risk factors leading to SCC development in these two conditions are different, molecular analyses have uncovered genetic and clinical similarities between these two SCC types.  

The rareness of RDEB and OTR tumors restricts the research and development for new therapeutic drugs. Therefore, researchers at the EB House have utilized a computer-based method (= in silico) to identify drugs already approved for other diseases that could also be effective in the treatment of SCC (= repurposing of drugs). By virtually screening a large number of substances against SCC, the time and cost of developing new drugs is significantly reduced.

In this project, the genetic similarities between tumors from organ transplant recipients and RDEB patients were determined and matched with data already available for the more prominent and also very aggressive head and neck SCC. The results specifically highlighted the de-regulation of specific molecular pathways in the SCC cells. The researchers assumed that tumor cells can be treated by targeting cancer-specific key molecules with defined drugs. In order to find a suitable drug, they conducted a large-scale in silico screening of publicly available data on small drug compounds. The virtual screening led to the identification of several drug candidates that could be used against SCC in RDEB. So far, however, this approach is completely virtual and the efficacy of the selected drugs needs to be confirmed in laboratory experiments.

Nevertheless, this study implemented a novel computational screening method, which will advance the development of cancer treatments for patients with rare and particularly aggressive SCC.

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