Targeting class I histone deacetylases in cancer therapy
Bibliographic record
Abstract
INTRODUCTION: Class I histone deacetylases (HDACs) are often overexpressed in cancer, and their inhibition typically leads cancer cells, but not normal cells, to apoptosis. Hence, the field of cancer therapy has experienced a continued surge in the development of HDAC inhibitors. AREAS COVERED: Class I comprises of HDAC1, 2, 3 and 8. HDAC1, 2 and 3 are active as subunits of multiprotein complexes while an HDAC8 complex has not been identified. Besides being a major contributor to poor prognosis in childhood neuroblastoma, little is known of HDAC8 functions and substrates. The targeting and activities of HDAC1 - 3 are modulated by post-translational modifications and association with numerous proteins. The composition of the various HDAC complexes is cell type dependent and fluctuates with intra- and intercellular stimuli. These HDAC complexes play roles at multiple levels in gene expression and genome stability. The application of isoform-specific HDAC inhibitors has met with varying success in clinical trials. EXPERT OPINION: To elucidate the mechanism and cellular impact of HDAC inhibitors, we need to identify the spectrum of class I HDAC complexes and their functions. In the cases of HDAC1 - 3, selectivity of HDAC inhibitors should be directed against relevant complexes. HDAC8 active site unique features facilitate the design of selective inhibitors.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".