{"id":5235,"date":"2019-10-22T17:35:32","date_gmt":"2019-10-22T15:35:32","guid":{"rendered":"https:\/\/www.iegt-rostock.de\/projekte_iegt\/dnp73-igf1r-projekt\/"},"modified":"2020-09-03T11:30:47","modified_gmt":"2020-09-03T09:30:47","slug":"dnp73-igf1r-projekt","status":"publish","type":"projekte_iegt","link":"https:\/\/www.iegt-rostock.de\/en\/projekte_iegt\/dnp73-igf1r-projekt\/","title":{"rendered":"Application of a DNp73-IGF1R signaling-based systems model for the prediction of metastasis probability and therapy responses in malignant melanoma"},"content":{"rendered":"

Application of a DNp73-IGF1R signaling-based systems model for the prediction of metastasis probability and therapy responses in malignant melanoma<\/h1>\n<\/div><\/div>

Our group provided first functional evidence that oncogenic DNp73 variants are crucial to initiate BRAF\/NRAS\/p53mut-independent melanoma invasion via the EPLIN-IGF1R\/AKT axis, and identified a multilevel DNp73-governed regulatory network that specifically controls malignant progression. This opens up completely new possibilities for the treatment of aggressive melanoma. Due to the DNp73-network complexity, holding multiple overlapping nonlinear regulatory motifs, we apply a computational systems model to determine molecular fingerprints allowing patient-stratified therapies and the discovery of novel drug targets. For this purpose, we developed a mathematical model that allows to consider the interpatient heterogeneity for metastasis-targeted strategiesto generate molecular signatures reflecting early metastatic spread and drug resistance. Based on validated simulated signatures, we will design multimodal patient-tailored therapies using CRISPR-Cas9 knockout\/activation strategies, in vivo LNAs, miR-mimics and clinically applied kinase inhibitors, which will be tested in established mouse metastasis models. The overall goal of this project is to provide DNp73-driven biomarker constellations that predict metastasis initiation and resistance probabilities, and to develop novel individual treatment paradigms.<\/span><\/p>\n<\/div><\/div>

<\/i><\/div>

Applicant<\/strong><\/p>\n

Prof. Brigitte P\u00fctzer M.D., Ph.D.
\nRostock University Medical Center
\nInstitute of Experimental Gene Therapy and Cancer Research<\/p>\n<\/div><\/div>

<\/i><\/div>

Research Partners<\/strong><\/p>\n

Prof. Jens Timmer Ph.D.
\nFaculty of Mathematics and Physics
\nBIOSS Centre for Biological Signaling Studies
\nInstitute of Physics
\nFreiburg im Breisgau<\/p>\n

PD Friederike Egberts M.D.
\nUniversity Hospital Schleswig-Holstein, Campus Kiel
\nDepartment of Dermatology<\/p>\n<\/div><\/div>

This project is funded by the German Cancer Aid (Deutsche Krebshilfe) 70112353<\/strong>.<\/p>\n<\/div><\/div><\/div><\/div><\/div>

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