WP 5 will functionally characterize events and phenotypes associated with ITH in FDS. In WP 1, PSMs of tumors characterized in SPs 1 and 2, as well as isogenic cell lines and mouse models bearing ITH candidates, will be established to enable the development of therapies based on functional profiling and mechanistic analyses of primary and treatment-induced plasticity and ITH. In work package 2, the different models will be used to predict the causes of treatment failure in the respective patients and to identify drug sensitivity and genetic susceptibilities to overcome resistance. In addition, based on the results obtained in WPs 1-4, tailored functional studies will be performed to identify events that impact malignant phenotypes such as proliferation and survival. In WP 3, detailed mechanistic investigation of specific ITH-related alterations or signaling pathways will unravel their biological relevance and impact on drug sensitivity and resistance.

Co-PI: Claudia Ball, DKFZ and NCT/UCC Dresden, Fetscherstraße 74, Dresden
PI: Ana Banito, DKFZ and KiTZ, Im Neuenheimer Feld 280, Heidelberg