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Record W4214592576 · doi:10.1080/14728222.2022.2047178

Calpain as a therapeutic target in cancer

2022· review· en· W4214592576 on OpenAlex

Why this work is in the frame

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

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueExpert Opinion on Therapeutic Targets · 2022
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCalpain Protease Function and Regulation
Canadian institutionsQueen's University
FundersCanadian Institutes of Health Research
KeywordsCalpainCancerMedicineCancer researchBiologyComputational biologyPharmacologyInternal medicineBiochemistryEnzyme

Abstract

fetched live from OpenAlex

INTRODUCTION: Calpain-1 and calpain-2 are prototypical classical isoforms of the calpain family of calcium-activated cysteine proteases. Their substrate proteins participate in a wide range of cellular processes, including transcription, survival, proliferation, apoptosis, migration, and invasion. Dysregulated calpain activity has been implicated in tumorigenesis, suggesting that calpains may be promising therapeutic targets. AREAS COVERED: This review covers clinical and basic research studies implicating calpain-1 and calpain-2 expression and activity in tumorigenesis and metastasis. We highlight isoform specific functions and provide an overview of substrates and cancer-related signalling pathways affected by calpain-mediated proteolytic cleavage. We also discuss efforts to develop clinically relevant calpain specific inhibitors and spotlight the challenges facing inhibitor development. EXPERT OPINION: Rationale for targeting calpain-1 and calpain-2 in cancer is supported by pre-clinical and clinical studies demonstrating that calpain inhibition has the potential to attenuate carcinogenesis and block metastasis of aggressive tumors. The wide range of substrates and cleavage products, paired with inconsistencies in model systems, underscores the need for more complete understanding of physiological substrates and how calpain cleavage alters their functions in cellular processes. The development of isoform specific calpain inhibitors remains an important goal with therapeutic potential in cancer and other diseases.

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.

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 categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.994
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.064
GPT teacher head0.378
Teacher spread0.315 · 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