Project Details
Projekt
Modelling and targeting bone metastasis formation in prostate cancer
Applicants
Miodrag Guzvic, Ph.D.; Professor Dr. Christoph Klein
Subject Area
Pathology
Hematology, Oncology
Hematology, Oncology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 491717755
All patients with metastatic prostate cancer in the bones die within 15 years after diagnosis of primary tumors. Currently, it is not possible, at diagnosis or during adjuvant therapy, to predict which patients will progress. Disseminated cancer cells lodging in bone marrow contain founder cell of later arising metastasis. Targeting these cells is sine qua non to prevent or delay death due to metastasis. However, due to their rarity, the biology of prostate cancer DCCs remained elusive. We have shown that prostate cancer DCCs adapt to the bone marrow microenvironment by assuming mixed epithelial/hematopoietic phenotype. Therefore, in order to improve current therapeutic approaches, we started generating a humanized and personalized in vitro 3D model of bone marrow to study early steps of bone colonization. Using the data from our molecular analysis of patient-derived DCCs, we will identify candidate pathways for therapeutic targeting. We will study and manipulate these pathways using the in vitro bone marrow model and eventually perform a drug screen. Finally, we will validate these finding by studying cancer progression in existing cohort of patients, ultimately aiming to develop an assay that predicts bone metastasis and therapy response.
DFG Programme
Priority Programmes
