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Record W4384029604 · doi:10.1093/noajnl/vdad071.016

ACQUIRED PTEN LOSS MAY MEDIATE DABRAFENIB AND TRAMETINIB RESISTANCE IN BRAF V600E–MUTATED EPITHELIOID GLIOBLASTOMA: A CASE REPORT

2023· article· en· W4384029604 on OpenAlexaff
Abrar Ahmed, Liana Nobre, Warren Mason, Julie Bennett, Uri Tabori, Cynthia Hawkins, Seth Climans

Bibliographic record

VenueNeuro-Oncology Advances · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMelanoma and MAPK Pathways
Canadian institutionsWestern University
Fundersnot available
KeywordsTrametinibDabrafenibPTENTemozolomideMedicineCancer researchVemurafenibMelanomaMEK inhibitorOncologyPI3K/AKT/mTOR pathwayGliomaInternal medicineBiologyMAPK/ERK pathwayMetastatic melanomaSignal transduction

Abstract

fetched live from OpenAlex

Abstract Epithelioid glioblastoma is a rare variant of glioblastoma that primarily affects children and young adults. This commonly has a BRAF V600E mutation and can be treated with BRAF and MEK inhibitors. CASE DESCRIPTION: An 18-year-old woman was diagnosed with an epithelioid glioblastoma. She received temozolomide chemoradiotherapy. Upon progression she had redo surgery and received dabrafenib and trametinib. The patient developed a drop metastasis to the cervical spine, and consequently received focal radiotherapy, 20 Gy in five fractions. Treatments were halted six months after her second resection due to further disease progression. She developed uncal herniation, requiring her to have a third resection approximately six months after her second resection. She passed away after this, 12 months following her initial diagnosis. Retrospective genetic analysis of three tumor specimens showed a novel PTEN mutation that arose after her first surgery. We suspect that the acquired PTEN mutation conferred resistance to dabrafenib and trametinib. DISCUSSION: This case offers teaching points and research questions. Firstly, early treatment with BRAF and MEK inhibitors in high grade BRAF V600E–mutated gliomas may be optimal as the patient may have stabilized with earlier treatment on dabrafenib and trametinib. Secondly, further studies are required to investigate whether the addition of PTEN mutation to BRAF V600E leads to aggressive tumor behavior. Lastly, there is a need for investigation into potential benefits of treating similar patients by co-targeting the BRAF and PI3K/AKT pathways.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.585
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
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)

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 head0.011
GPT teacher head0.284
Teacher spread0.273 · 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.

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

Citations1
Published2023
Admission routes1
Has abstractyes

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