Systems biology of the Unfolded Protein Response in Glioma
Glioma belong to the most common primary tumors of the brain. Glioblastoma is the most commonly diagnosed and the most aggressive malignant brain tumor. Despite multiple forms of treatment options (surgery, radiation treatment and chemotherapy), the median survival rate of patients with this form of brain cancer is about 14 months. One important reason for the poor prognosis is the aggressive growth of these tumor cells as they infiltrate the surrounding brain tissues. As a result, performing a complete surgical resection of the area is not possible. The remaining tumor cells have proven themselves to be extremely resistent against further therapeutic methods, such as radiation and chemotherapy. Relapse often occurs as a result. The invasion of the surrounding healthy brain tissues by glioma tumors does not happen randomly. It has been found to be associated with distinct anatomic structures such as the basement membranes of blood vessels as well as the subependyma. With regards to migration and invasion, the inhibitory myelin pathways also serve as essential structures for glioma in non-glioma cells (neurons, fibroblasts, other tumor cells as well as CNS metastases). The currently used standard therapies, such as radio and alkylating chemotherapy (including Temodal), target dividing cells. However, the invading cells do not divide, since the responsible components of the cytoskeleton direct mobility and cell division mechanisms, but not both at the same time (“go or grow” hypothesis). These cells are therefore therapy-resistant, which creates a major problem for treatment. New therapeutic agents can help stop the invasion and make the cells more susceptible to established therapeutic methods. In this connection, the Unfolded Protein Response shows great potential as a goal for therapeutic interventions.
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Keywords: Unfolded Protein Response