BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Targeting bromodomain and extra-terminal domain (BET) proteins has shown a promising therapeutic effect on melanoma. The development of strategies to better kill melanoma cells with BET inhibitor treatment may provide new clinical applications. Here, we used a drug synergy screening approach to combine JQ1 with 240 antitumor drugs from the Food and Drug Administration (FDA)-approved drug library and found that sunitinib synergizes with BET inhibitors in melanoma cells. We further demonstrated that BET inhibitors synergize with sunitinib in melanoma by inducing apoptosis and cell cycle arrest. Mechanistically, BET inhibitors sensitize melanoma cells to sunitinib by inhibiting GDF15 expression. Strikingly, GDF15 is transcriptionally regulated directly by BRD4 or indirectly by the BRD4/IL6/STAT3 axis. Xenograft assays revealed that the combination of BET inhibitors with sunitinib causes melanoma suppression in vivo. Altogether, these findings suggest that BET inhibitor-mediated GDF15 inhibition plays a critical role in enhancing sunitinib sensitivity in melanoma, indicating that BET inhibitors synergize with sunitinib in melanoma.
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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 it