P45 | TARGETING PRELAMIN A PROCESSING TO SENSITIZE GLIOBLASTOMA CELLS TO OXIDATIVE STRESS
Glioblastoma is the most common and aggressive tumor of the Central Nervous System, with limited therapeutic options and poor prognosis. Current standard treatments (surgical resection, radiotherapy, and chemotherapy) offer only marginal improvements in patient survival, underscoring the urgency of...
Saved in:
| Format: | Article |
|---|---|
| Language: | English |
| Published: |
PAGEPress Publications
2025-08-01
|
| Series: | European Journal of Histochemistry |
| Subjects: | |
| Online Access: | https://www.ejh.it/ejh/article/view/4367 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Glioblastoma is the most common and aggressive tumor of the Central Nervous System, with limited therapeutic options and poor prognosis. Current standard treatments (surgical resection, radiotherapy, and chemotherapy) offer only marginal improvements in patient survival, underscoring the urgency of developing novel therapeutic strategies. In this study, it was explored an innovative approach that interferes with the processing of lamin A precursor, prelamin A, in glioblastoma cells. Specifically, farnesyltransferase activity was inhibited using SCH66336 (Lonafarnib), leading to intracellular accumulation of prelamin A. This accumulation mimics a «laminopathic» phenotype -similar to that observed in systemic progeroid syndromes caused by defects in lamin A processing1- selectively induced in glioblastoma cells, which, unlike healthy brain tissue, express high levels of lamin A2. The resulting nuclear dysfunction sensitizes glioblastoma cells to oxidative stress triggered by Menadione, while having minimal effects on normal human astrocytes. The combined treatment with SCH66336 and Menadione significantly reduced proliferation, altered the expression of key stemness markers, and compromised the viability of glioblastoma stem cells (GSCs) derived from patients - cells known to drive tumor progression and resistance to therapy. These results suggest that targeting prelamin A processing could represent a promising adjunctive strategy to attenuate glioblastoma aggressiveness, particularly by impairing therapy-resistant GSC populations3. This dual-hit approach may pave the way for more effective combination therapies in the clinical management of glioblastoma.
|
|---|---|
| ISSN: | 1121-760X 2038-8306 |