YAP1 İNHİBİSYONUNUN BEYİN KANSERİ VE BEYİN KANSERİ KÖK HÜCRELERİ ÜZERİNDEKİ MOLEKÜLER ETKİSİNİN ARAŞTIRILMASI
Project no. 21886 · Status: Kapanmış (Yayın bekleniyor) · 2020
Summary
Glioblastoma is the most common and most aggressive primary brain tumor in adults. The survival time of 3-5% of the patients in whom standard treatment protocols are applied for 12- 15 months can be extended up to 5 years. With the latest developments in next-generation sequencing methods, specific molecular markers such as MGMT, IDH, EGFR, VEGF, TP53, PTEN, p16INK4a genes, phospholipid metabolites and cancer stem cells have been routinely identified in the clinic to partially understand the molecular pathogenesis of the disease and provide potential diagnostic, prognostic and predictive effects. biomarkers have been identified, but increasing therapeutic efficacy remains a major challenge in GBM treatment. Especially in cancer stem cells, signaling pathways that include some target molecules with various genetic and epigenetic aberrations that can be effective on rootedness resistance mechanisms constitute important focal points. While clinical studies on signaling pathways such as NOTCH and WNT continue, the Hippo signal transduction pathway and its transcriptional regulators YAP/TAZ, which are active in the embryonic period with their remarkable biological properties in differentiation, stem cell self-renewal, tissue homeostasis and cancer, constitute a new focus. A comprehensive analysis of brain tumor samples by immunohistochemistry determined that the expression of YAP is increased in a variety of human brain tumors, particularly infiltrative astrocytomas, oligodendrogliomas, and GBM. Strikingly, YAP expression is significantly higher in the mesenchymal subtype of GBM and is more aggressive and associated with poorer prognosis when associated with gliomas. In this study, YAP1, which is known to be overexpressed in glioblastomas, was targeted and silenced with siRNA in brain cancer and brain cancer stem cells in order to determine its potential as an alternative treatment target, and the therapeutic potential of a newly developed YAP1 inhibitor CA3 (CIL56) was investigated in vitro with advanced molecular analyzes.