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Record W2396152701 · doi:10.1158/1557-3265.ovca15-ia06

Abstract IA06: Regulation of BRCA1- and BRCA2-dependent DNA repair.

2016· article· en· W2396152701 on OpenAlexaff
Daniel Durocher

Bibliographic record

VenueClinical Cancer Research · 2016
Typearticle
Languageen
FieldMedicine
TopicPARP inhibition in cancer therapy
Canadian institutionsLunenfeld-Tanenbaum Research Institute
Fundersnot available
KeywordsOlaparibPALB2Synthetic lethalityDNA repairCancer researchPARP inhibitorHomologous recombinationOvarian cancerCancerDNA damagePoly ADP ribose polymeraseBRCA2 ProteinMedicineBiologyPolymeraseMutationDNAGeneticsGeneGermline mutation

Abstract

fetched live from OpenAlex

Abstract High-grade serous epithelial ovarian cancers are strongly associated with defective homologous recombination (HR), a DNA repair pathway involved in the mending of DNA double-strand breaks (DSB) and in which the BRCA1, PALB2 and BRCA2 tumor suppressors play key roles. In late December last year, the first poly(ADP-ribose) polymerase (PARP) inhibitor, lynparza or olaparib as it is widely known was approved in Europe and in the US for the treatment of ovarian cancer in tumors with deleterious mutations in the BRCA1 and BRCA2 genes. The approval of olaparib marks a milestone in the development of targeted cancer therapies, as it is the first approved drug that is based on the concept of synthetic lethality. In my presentation, I will report the identification of a system that licenses the assembly of a BRCA1-PALB2-BRCA2 complex in the S and G2 phases of the cell cycle. This system plays a major role in restricting the activation of DNA repair by HR to these cell cycle phases and I will discuss the implication of this newly discovered regulatory pathway to our understanding of genome maintenance and PARP inhibitor therapy. Citation Format: Daniel Durocher. Regulation of BRCA1- and BRCA2-dependent DNA repair. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr IA06.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.007
Threshold uncertainty score0.023

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0020.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0070.004

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 head0.292
GPT teacher head0.553
Teacher spread0.261 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
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

Citations0
Published2016
Admission routes1
Has abstractyes

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