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Management of Metabolic Effects Associated With Anticancer Agents Targeting the PI3K-Akt-mTOR Pathway

2012· article· en· 231 citations· W2107561358 on OpenAlex· 10.1200/jco.2011.39.7356

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.

Full frame distilled prediction

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.

Candidate categories
none
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: ObservationalConsensus signal: Observational
Genre
Candidate signal: EmpiricalConsensus signal: Empirical
Teacher disagreement score
0.364
Threshold uncertainty score
0.405
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0040.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

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.

Opus teacher head0.053
GPT teacher head0.403
Teacher spread
0.350 · how far apart the two teachers sit on this one work
Validation status
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

Abstract

Agents inhibiting the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin (PAM) pathway are currently in various stages of clinical development in oncology, ranging from some in early-phase evaluations to others that have already received regulatory approval for treatment in advanced cancers. The administration of PAM pathway inhibitors has been associated with metabolic toxicities of hyperlipidemia and hyperglycemia. The PAM Task Force of the National Cancer Institute Investigational Drug Steering Committee convened an interdisciplinary expert panel to review the pathophysiology of hyperlipidemia and hyperglycemia induced by PAM pathway inhibitors, summarize the incidence of these metabolic toxicities induced by such agents in the current literature, advise on clinical trial screening and monitoring criteria, and provide management guidance and therapeutic goals on occurrence of these toxicities. The overarching aim of this consensus report is to raise awareness of these metabolic adverse events to enable their early recognition, regular monitoring, and timely intervention in clinical trials. Hyperglycemia and hyperlipidemia are generally not acutely toxic and most often reversible with therapeutic intervention. Dose modifications or discontinuation of PAM pathway inhibitors should only be considered in situations of severe events or if progressive metabolic derangement persists after therapeutic interventions have been attempted for a sufficient duration. Specialty consultation should be sought to aid clinical trial planning and the management of these metabolic adverse events.

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.

The record

Venue
Journal of Clinical Oncology
Topic
PI3K/AKT/mTOR signaling in cancer
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Princess Margaret Cancer CentreOntario Institute for Cancer Research
Funders
National Cancer Institute
Keywords
MedicinePI3K/AKT/mTOR pathwayAdverse effectClinical trialDiscontinuationHyperlipidemiaPharmacologyIntensive care medicineBioinformaticsInternal medicineSignal transductionDiabetes mellitusEndocrinology
Has abstract in OpenAlex
yes