Project B11
Towards Personalised Treatment Strategies for Aggressive PPGLs
Project B11 of the CRC/Transregio 205 focuses on improving therapeutic options for aggressive and metastatic pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors with limited treatment possibilities and poor prognosis in advanced stages. Building on unique expertise and model systems developed in previous funding periods, the project aims to translate molecular insights into clinically relevant, personalized treatment strategies.
A central strength of the project is the establishment and systematic use of advanced preclinical models, including primary patient-derived (ppd) cultures, 3D tumor systems, genetically engineered models, and the first human patient-derived xenograft (PDX) of metastatic PPGL. These models closely reflect human tumor biology and enable functional testing of therapeutic vulnerabilities that cannot be addressed in conventional systems.
The current funding period focuses on three major goals: identifying predictive biomarkers and kinase signaling signatures that determine therapy response, evaluating novel therapeutic strategies for aggressive PPGLs, and translating these findings into personalized treatment concepts.
Specific aims:
(I) Examine HSP90 inhibition as a strategy to block Ras/Raf/ERK pathway overactivation and overcome RTKi resistance
(II) Translate next-generation personalised multi-drug testing in ppd-PPGLs to the clinic, and identify personalised kinase activation patterns to predict therapy responses
(III) Explore the role of NDUFA4L2 as therapeutic target in P-PPGL
| Principal Investigators | Institution |
| Prof. Dr. med. Svenja Nölting | LMU |
| Prof. Dr. rer. nat. Natalia S. Pellegata | HMGU |
| Dr. rer. nat. Hermine Mohr | HMGU |
