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Record W2794019434 · doi:10.1073/pnas.1719760115

Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers

2018· article· en· W2794019434 on OpenAlexaff
Masanori Kawakami, Lisa Maria Mustachio, Lin Zheng, Yulong Chen, Jaime Rodriguez‐Canales, Barbara Mino, Jonathan M. Kurie, Jason Roszik, Pamela Villalobos, Kelsie L. Thu, Jennifer Silvester, David W. Cescon, Ignacio I. Wistuba, Tak W. Mak, Xi Liu, Ethan Dmitrovsky

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrotubule and mitosis dynamics
Canadian institutionsUniversity of TorontoPrincess Margaret Cancer CentreUniversity Health Network
FundersNational Cancer InstituteNational Institutes of Health
KeywordsCentrosomeMitosisPolo-like kinaseBiologyMitotic catastropheCancer researchKinaseCentrosome cycleCell biologyCell cycleCancerGenetics

Abstract

fetched live from OpenAlex

Significance Despite current treatments, lung cancers remain a major public health problem. Innovative ways are needed to treat or prevent these cancers. Centrosomes are critical for fidelity of mitosis. Abnormal centrosome numbers can cause aberrant mitosis and cell death. Polo-like kinase 4 (PLK4) regulates centriole duplication, and its deregulation alters centrosome number and mitosis. The potent PLK4 inhibitor CFI-400945 is reported here to exert marked antineoplastic effects against lung cancers. CDK2 inhibition also deregulates mitosis and was found to cooperate with PLK4 antagonism. CFI-400945 is now undergoing phase I clinical trial testing (NCT01954316). Taken together, targeting PLK4 for inhibition holds promise in lung cancer therapy either as a single agent or when combined with an agent that deregulates mitosis.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score0.291

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.018
GPT teacher head0.285
Teacher spread0.267 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations87
Published2018
Admission routes1
Has abstractyes

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