Leeomic: A comprehensive proteomic analysis towards discovery of predictive patterns of protein expression to ribociclib sensitivity and resistance—A compLEEment-1 Canadian correlative sub-study.
Bibliographic record
Abstract
TPS3170 Background: Despite developments in the treatment of advanced hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer, primary or acquired resistance eventually occurs in all cases and there is still very limited understanding of the mechanisms of resistance to therapy. LEEOMIC is a sub-study of the main CompLEEment-1 ( N = 3255 patients enrolled, CLEE011A2404 v03) trial, an open-label, phase 3b study evaluating ribociclib + letrozole as first-line therapy in an expanded advanced breast cancer patient population which recruited over 250 Canadian patients. The purpose of this Canadian correlative sample collection study is to explore the mechanisms of response and resistance to ribociclib in combination with letrozole through proteomic and ctDNA analysis. Methods: The British Columbia Cancer Research Centre team developed a novel and optimized MS/MS platform called SP3-Clinical Tissue Proteomics (SP3-CTP) to perform in-depth proteome profiling ( > 8,000 proteins) from formalin fixed paraffin embedded (FFPE) material (10-micron section). SP3-CTP analysis of the proteome of the study patients who did not achieve clinical benefit (primary resistance: progression within 3 months of treatment) will be compared to the proteome of the sub-group of prolonged responders (time to progression of 22 months or more) in order to identify biomarkers that can predict response or de-novo resistance to therapy. Archival tumor biopsies (primary or metastatic) collected from the study will be submitted for proteomic analysis to identify proteomic expression levels that may serve as predictor of response. It is anticipated that over 150 samples will be collected. If available, blood samples taken at time of progression or end of treatment will also be analyzed for ctDNA for genetic profiling and to study if there is any correlation between genetic mutations and response or resistance to therapy. Currently, both tissue and blood samples are being collected and no analysis has been conducted thus far. Clinical trial information: NCT03613220.
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 imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".