ArticleCPT: pharmacometrics & systems pharmacology2015
Model-Based Design of a Decision Tree for Treating HER2+ Cancers Based on Genetic and Protein Biomarkers.
Article in CPT: pharmacometrics & systems pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Reproducibility of Quantitative Systems Pharmacology Models: Current Challenges and Future Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Review
- Tensor clustering with algebraic constraints gives interpretable groups of crosstalk mechanisms in breast cancer.Journal of the Royal Society, Interface · 2019Article
- Clinical responses to ERK inhibition inNPJ systems biology and applications · 2017Article
- HER2+ Cancer Cell Dependence on PI3K vs. MAPK Signaling Axes Is Determined by Expression of EGFR, ERBB3 and CDKN1B.PLoS computational biology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cancers are incredibly diverse with regard to molecular aberrations, dependence on oncogenic signaling pathways, and responses to pharmacological intervention. We wished to assess how cellular dependence on the canonical PI3K vs. MAPK pathways within HER2+ cancers affects responses to combinations of targeted therapies, and biomarkers predictive of their activity. Through an integrative analysis of mechanistic model simulations and in vitro cell line profiling, we designed a six-arm decision tree to stratify treatment of HER2+ cancers using combinations of targeted agents. Activating mutations in the PI3K and MAPK pathways (PIK3CA and KRAS), and expression of the HER3 ligand heregulin determined sensitivity to combinations of inhibitors against HER2 (lapatinib), HER3 (MM-111), AKT (MK-2206), and MEK (GSK-1120212; trametinib), in addition to the standard of care trastuzumab (Herceptin). The strategy used to identify effective combinations and predictive biomarkers in HER2-expressing tumors may be more broadly extendable to other human cancers.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.