Effect of histone deacetylase and proteasome inhibitors in glioma models
Effect of histone deacetylase and proteasome inhibitors in glioma models
Gliomas, and especially glioblastoma (GB), are among the most aggressive brain tumors, usually leading to a very poor outcome for patients. Despite decades of research, current treatments - mainly surgery followed by chemotherapy and radiotherapy - have only modestly improved survival. This highlights the urgent need for better therapies.
The main goal of this thesis of Luciana Costa Furtado was to explore whether two types of drugs - histone deacetylase inhibitors (HDACi) and proteasome inhibitors (PI - could be effective against gliomas. HDACi work by changing how genes are turned on or off, while PI block the proteasome, the cell’s machinery for breaking down proteins, causing proteins to build up inside the cell. Because both disrupt essential cell processes, using them together could have a powerful effect against tumor cells. We also investigated whether it is possible to design more specific HDACi to make them safer and more effective. At the same time, we studied how these drugs, alone and in combination, kill glioma cells and glioblastoma stem cells (GSCs), which are thought to drive tumor growth and resistance.
Since these treatments increase the stress caused by protein buildup, we focused on the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR - cellular systems that try to restore protein balance but can also trigger cell death when overwhelmed.