NU22-03-00318 Strategies for specific targeting of brain metastasis microenvironment for diagnostic and therapy
Brain metastases affect approximately 20% of patients with various solid cancers and are the most common malignant tumors of the central nervous system in adults. This project focuses on Fibroblast activation protein (FAP) as a new potential diagnostic and therapeutic target in brain metastases. It aims to determine the quantity and localization of FAP in brain metastases of various origins, establish clinically relevant in vivo models and prepare and use original highly specific low molecular weight ketoamide FAP inhibitors as targeting ligands for sensitive detection of metastatic lesions and delivery of therapeutic agents.
GAUK 342522 The role of cancer-associated fibroblasts in the microenvironment of brain metastases from non-small cell lung cancer
Brain metastases are a frequent complication of non-small cell lung cancer. A key factor contributing to the progression and therapeutic resistance, but at the same time a potential therapeutic target in many cancers is cancer-associated stroma, comprising among others of cancer associated fibroblasts (CAFs). The aim of the project is to determine the role of CAF-like cells in the progression of brain metastases from NSCLC via their interaction with malignant and immune cells.
GAUK 365022 FAP positive mesenchymal cells and T cell response in glioblastoma
Glioblastomas are aggressive brain tumors characterized by strong systemic and local immunosuppression. T lymphocytes are one of the main components of the anti-tumor immune response, but in the tumor microenvironment they often acquire an exhausted phenotype manifested by their dysfunction, long-term expression of immune system checkpoint molecules, and suppressed effector response. The aim of the project is to describe the effect of soluble factors and cell-cell contacts of glioblastoma associated mesenchymal cells expressing fibroblast activation protein on the activation, production of cytotoxic molecules, apoptosis, and expression of immune checkpoint molecules of T lymphocytes.