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Record W1977983810 · doi:10.1016/s0960-9776(11)70295-8

Reappraising antiangiogenic therapy for breast cancer

2011· review· en· W1977983810 on OpenAlex
Robert S. Kerbel

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

VenueThe Breast · 2011
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAngiogenesis and VEGF in Cancer
Canadian institutionsUniversity of Toronto
FundersNational Cancer InstituteNational Institutes of HealthNational Health Research InstitutesCanadian Cancer Society Research InstituteCanadian Institutes of Health ResearchNational Institute for Health and Care ResearchCanada Research ChairsGlaxoSmithKlinePfizer CanadaCancer Research Institute
KeywordsMedicineBevacizumabSunitinibBreast cancerOncologyChemotherapyMetastatic breast cancerInternal medicineCancerAngiogenesisTrastuzumabClinical trialPharmacology

Abstract

fetched live from OpenAlex

Phase III trials of antiangiogenic drugs for metastatic breast cancer have either had only limited success, e.g. the monoclonal anti-VEGF antibody bevacizumab when used with various conventional chemotherapy regimens, or have failed altogether, e.g. the small molecule oral tyrosine kinase inhibitor (TKI) sunitinib. No phase III trial has yet demonstrated an overall survival benefit and the progression free survival (PFS) benefits, when attained with bevacizumab are short, with perhaps one exception. Together, these results call for a reappraisal of using antiangiogenic drugs for breast cancer and possible strategies to improve their efficacy. Among the reasons to help explain the limited benefits observed thus far include the possibility that angiogenesis may not be a major driver of breast cancer growth, compared to some other types of cancer; that acquired resistance may develop rapidly to VEGF-pathway targeting antiangiogenic drugs, in part due to angiogenic growth factor redundancy; that optimal chemotherapy regimens have not been used in conjunction with an antiangiogenic drug; and that antiangiogenic drugs may secondarily aggravate biologic aggressiveness of the tumors, thereby reducing their overall efficacy after inducing an initial benefit. Several possible strategies are discussed for improving the efficacy of antiangiogenic drugs, including combination with different chemotherapy regimens, e.g. long term and less toxic metronomic chemotherapy protocols; validation of predictive biomarkers to individualize patient therapy; development of improved preclinical therapy models, e.g. involving advanced metastatic breast cancer, and combination with other types of anti-cancer agents especially biologies such as trastuzumab for Her2-positive breast cancer. Reasons for the current concern regarding use of antiangiogenic drug treatments for early stage cancers, including breast cancer, are also discussed.

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)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.991
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.056
GPT teacher head0.347
Teacher spread0.291 · 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