Hau, Peter and Jachimczak, Piotr and Schlaier, Juergen and Bogdahn, Ulrich (2011) TGF-beta 2 Signaling in High-Grade Gliomas. CURRENT PHARMACEUTICAL BIOTECHNOLOGY, 12 (12). pp. 2150-2157. ISSN 1389-2010, 1873-4316
Full text not available from this repository. (Request a copy)Abstract
High-grade gliomas are the most common primary tumors in the central nervous system (CNS) in adults. Despite efforts to improve treatment by combination therapies (neurosurgery, radio- and chemotherapy), high-grade glioma patients still have a grim prognosis, indicating an urgent need for new therapeutic approaches. The molecular processes of gliomagenesis are being unraveled, and novel targeted therapeutic strategies to defy high-grade gliomas are emerging. Transforming growth factor-beta (TGF-beta), in particular the TGF-beta 2 isoform, has been identified as a key factor in the progression of malignant gliomas. TGF-beta 2, originally described as "glioblastoma-derived T-cell suppressor factor", is associated with the immuno-suppressed status of patients with glioblastoma, and is therefore responsible for loss of tumor immune surveillance. Elevated TGF-beta 2 levels in tumors and in the plasma of patients have been associated with advanced disease stage and poor prognosis. Consequently, a targeted strategy to modulate TGF-beta 2 signaling is highly promising. The antisense oligonucleotide trabedersen (AP 12009) that specifically blocks TGF-beta 2 mRNA will be the main focus of this review. In three phase I/II studies and a randomized, active-controlled dose-finding phase IIb study, trabedersen treatment of high-grade glioma patients with recurrent or refractory tumor disease led to long-lasting tumor responses and so far promising survival data. On the basis of these data the currently ongoing phase III study SAPHIRRE was initiated.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; REGULATORY T-CELLS; CANCER STEM-CELLS; HUMAN BRAIN-TUMORS; TGF-BETA; HUMAN GLIOBLASTOMA; NERVOUS-SYSTEM; TRANSFORMING GROWTH-FACTOR-BETA-2; SUPPRESSOR FACTOR; IMMUNE-RESPONSE; Transforming growth factor beta; signaling pathway; gliomagenesis; high-grade glioma; antisense; oligonucleotide |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurochirurgie Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Petra Gürster |
| Date Deposited: | 08 May 2020 06:24 |
| Last Modified: | 08 May 2020 06:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19695 |
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