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Record W3194110153 · doi:10.1016/j.cbpa.2021.07.004

Drugging the undruggable proteins in cancer: A systems biology approach

2021· review· en· W3194110153 on OpenAlexafffund
Shivanthy Pathmanathan, Ingrid Grozavu, Anna Lyakisheva, Igor Štagljar

Bibliographic record

VenueCurrent Opinion in Chemical Biology · 2021
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicUbiquitin and proteasome pathways
Canadian institutionsUniversity of Toronto
FundersGenentechCanadian Prostate Cancer Research InitiativeOntario Ministry of Economic Development, Job Creation and TradeCanadian Cancer SocietyFondation Brain CanadaCanadian Cancer Society Research InstituteCanadian Institutes of Health ResearchCancer Research SocietyQuébec Consortium for Drug DiscoveryGenome Canada
KeywordsComputational biologyDrug discoveryBiologySystems biologyComputer scienceData scienceBioinformatics

Abstract

fetched live from OpenAlex

In recent years, the research community has, with comprehensive systems biology approaches and related technologies, gained insight into the vast complexity of numerous cancers. These approaches allow an in-depth exploration that cannot be achieved solely using conventional low-throughput methods, which do not closely mimic the natural cellular environment. In this review, we discuss recent integrative multiple omics approaches for understanding and modulating previously identified 'undruggable' targets such as members of the RAS family, MYC, TP53, and various E3 ligases and deubiquitinases. We describe how these technologies have revolutionized drug discovery by overcoming an array of biological and technological challenges and how, in the future, they will be pivotal in assessing cancer states in individual patients, allowing for the prediction and application of personalized disease treatments.

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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.992
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.001
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 head0.118
GPT teacher head0.399
Teacher spread0.281 · 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 designNot applicable
Domainnot available
GenreReview

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

Citations31
Published2021
Admission routes2
Has abstractyes

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