Polo-like kinase 4 (PLK4) as a therapeutic target in breast cancer
Bibliographic record
Abstract
Polo-like kinase 4 (PLK4) is a key kinase regulating centriole duplication, centrosome maturation, cytokinesis and other cellular processes. Growing evidence suggests a critical role of PLK4 in the development and progression of various cancers. In many cancer types, its upregulation leads to pro-oncogenic phenotypes, while its pharmacologic inhibition leads to anticancer effects. Functionally, PLK4 affects cancer cell proliferation, growth, motility, invasion, migration, epithelial-mesenchymal transition, apoptosis and other critical oncogenic processes. In breast cancer, PLK4 is associated with centrosome amplification, aneuploidy and chromosomal instability, promoting invasive phenotypes and resistance to cancer cell death. PLK4 shows great promise as a prognostic and predictive biomarker in breast cancer. It is commonly found to be overexpressed in primary human breast cancers and is associated with poor oncologic outcomes, clinicopathologic parameters, and high-risk subtypes. Various compounds, such as CFI-400945, centrinone B, and others have been developed to inhibit PLK4 activity. Preclinical studies have shown that PLK4 inhibitors lead to decreased proliferation, growth and migration and increased breast cancer cell death. Moreover, PLK4 inhibition can serve to enhance the effects of other treatments, including radiotherapy. Clinical studies have been initiated with some of these compounds in cancer patients, including those with breast cancer. This manuscript discusses the role of PLK4 as a promising therapeutic target in breast cancer, one of the most common causes of morbidity and mortality in women.
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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) | 0.001 | 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 | 0.000 |
| 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".