Dovitinib enhances temozolomide efficacy in glioblastoma cells
Bibliographic record
Abstract
The multikinase inhibitor and FDA ‐approved drug dovitinib (Dov) crosses the blood–brain barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov‐mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target high‐mobility group protein A2 ( HMGA 2). The Dov‐induced reduction in pSTAT 3 Tyr705 phosphorylation demonstrated that Dov negatively affects the STAT 3/ LIN 28/Let‐7/ HMGA 2 regulatory axis in GB cells. Consistent with the known function of LIN 28 and HMGA 2 in GB self‐renewal, Dov reduced GB tumor sphere formation. Dov treatment also caused the downregulation of key base excision repair factors and O 6 ‐methylguanine‐ DNA ‐methyltransferase ( MGMT ), which are known to have important roles in the repair of temozolomide ( TMZ )‐induced alkylating DNA damage. Combined Dov/ TMZ treatment enhanced TMZ ‐induced DNA damage as quantified by nuclear γH2 AX foci and comet assays, and increased GB cell apoptosis. Pretreatment of GB cells with Dov (‘Dov priming’) prior to TMZ treatment reduced GB cell viability independent of p53 status. Sequential treatment involving ‘Dov priming’ and alternating treatment cycles with TMZ and Dov substantially reduced long‐term GB cell survival in MGMT + patient GB cells. Our results may have immediate clinical implications to improve TMZ response in patients with LIN 28 + / HMGA 2 + GB , independent of their MGMT methylation status.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".