ArticleCell cycle (Georgetown, Tex.)2010
The Raf/MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy.
Article in Cell cycle (Georgetown, Tex.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 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
75 citing papers in PubMed, 136 citations in OpenAlex.
- Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia.The Journal of clinical investigation · 2015Trial
- Activation of TP53 target genes in the primary response of triple-negative breast cancer cells to doxorubicin treatment.Scientific reports · 2025Article
- Thiazolidinedione derivatives: emerging role in cancer therapy.Molecular diversity · 2025Review
- Nanodroplet Array Platform for Integrated Synthesis and Screening of MEK Inhibitors: a Miniaturized Approach to Early Drug Discovery.Angewandte Chemie (International ed. in English) · 2025Article
- Article
- Fibroblast growth factor receptor expression in hemangioblastomas: A novel therapeutic target.PloS one · 2025Article
- Vitamin D Relieves Epilepsy Symptoms and Neuroinflammation in Juvenile Mice by Activating the mTOR Signaling Pathway via RAF1: Insights from Network Pharmacology and Molecular Docking Studies.Neurochemical research · 2024Article
- Research into overcoming drug resistance in lung cancer treatment using CRISPR-Cas9 technology: a narrative review.Translational lung cancer research · 2024Review
- Article
- Review
- Trametinib boosts palbociclib's efficacy in breast cancer via autophagy inhibition.Oncology research · 2024Article
- Titanium dioxide nanostructure-loaded Adriamycin surmounts resistance in breast cancer therapy: ABCA/P53/C-myc crosstalk.Future science OA · 2024Article
- Single-Cell Proliferation Microfluidic Device for High Throughput Investigation of Replicative Potential and Drug Resistance of Cancer Cells.Cellular and molecular bioengineering · 2023Article
- ERK Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro and In Vivo.Cancers · 2022Article
- Review
- Mutated RAS-associating proteins and ERK activation in relapse/refractory diffuse large B cell lymphoma.Scientific reports · 2022Article
- CXCR2 Small-Molecule Antagonist Combats Chemoresistance and Enhances Immunotherapy in Triple-Negative Breast Cancer.Frontiers in pharmacology · 2022Article
- Blockade of p38 MAPK overcomes AML stem cell line KG1a resistance to 5-Fluorouridine and the impact on miRNA profiling.PloS one · 2022Article
- Targeting Adenylate Cyclase Family: New Concept of Targeted Cancer Therapy.Frontiers in oncology · 2022Review
- Design, Synthesis, and Antileukemic Evaluation of a Novel Mikanolide Derivative Through the Ras/Raf/MEK/ERK Pathway.Frontiers in pharmacology · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
The effects of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways on proliferation, drug resistance, prevention of apoptosis and sensitivity to signal transduction inhibitors were examined in FL/DeltaAkt-1:ER*(Myr(+)) + DeltaRaf-1:AR cells which are conditionally-transformed to grow in response to Raf and Akt activation. Drug resistant cells were isolated from FL/DeltaAkt-1:ER*(Myr(+)) + DeltaRaf-1:AR cells in the presence of doxorubicin. Activation of Raf-1, in the drug resistant FL/DeltaAkt-1:ER*(Myr(+)) + DeltaRaf-1:AR cells, increased the IC(50) for doxorubicin 80-fold, whereas activation of Akt-1, by itself, had no effect on the doxorubicin IC50. However, Akt-1 activation enhanced cell proliferation and clonogenicity in the presence of chemotherapeutic drugs. Thus the Raf/MEK/ERK pathway had profound effects on the sensitivity to chemotherapeutic drugs, and Akt-1 activation was required for the long term growth of these cells as well as resistance to chemotherapeutic drugs. The effects of doxorubicin on the induction of apoptosis in the drug resistant cells were enhanced by addition of either mTOR and MEK inhibitors. These results indicate that targeting the Raf/MEK/ERK and PI3K/Akt/mTOR pathways may be an effective approach for therapeutic intervention in drug resistant cancers that have mutations activating these cascades.
Indexed as
Identifiers
What OpenQuestion holds
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.