ArticleBMC cancer2018
Rational development of synergistic combinations of chemotherapy and molecular targeted agents for colorectal cancer treatment.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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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.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Modulation of the Estrogen/erbB2 Receptors Cross-talk by CDK4/6 Inhibition Triggers Sustained Senescence in Estrogen Receptor- and ErbB2-positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
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- P38MAPK targeting in pancreatic ductal adenocarcinoma: Promising interventional approach for breaking drug resistance and tumor control.Medical oncology (Northwood, London, England) · 2026Article
- Polyphenols, Polysaccharides, and Their Complexes fromMolecules (Basel, Switzerland) · 2025Review
- Shining light on drug discovery: optogenetic screening for TopBP1 biomolecular condensate inhibitors.NAR cancer · 2025Article
- TopBP1 biomolecular condensates as a new therapeutic target in advanced-stage colorectal cancer.eLife · 2025Article
- ATR inhibition potentiates FOLFIRINOX cytotoxic effect in models of pancreatic ductal adenocarcinoma by remodelling the tumour microenvironment.British journal of cancer · 2025Article
- Article
- Review
- STING-ATF3/type I interferon crosstalk: A potential target to improve anti-tumour immunity in chemotherapy-treated urothelial carcinoma.Clinical and translational medicine · 2024Article
- Improving the response to oxaliplatin by targeting chemotherapy-induced CLDN1 in resistant metastatic colorectal cancer cells.Cell & bioscience · 2023Article
- Dibenzylideneacetone Induces Apoptosis in Cervical Cancer Cells through Ros-Mediated Mitochondrial Damage.Antioxidants (Basel, Switzerland) · 2023Article
- Article
- Plant-Derived Bioactive Compounds in Colorectal Cancer: Insights from Combined Regimens with Conventional Chemotherapy to Overcome Drug-Resistance.Biomedicines · 2022Review
- Review
- Clinical Benefit of Therapeutic Drug Monitoring in Colorectal Cancer Patients Who Received Fluorouracil-Based Chemotherapy.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges.World journal of gastrointestinal oncology · 2021Review
- Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics.Frontiers in oncology · 2020Review
- Phenotyping of Adaptive Immune Responses in Inflammatory Diseases.Frontiers in immunology · 2020Review
- A high-throughput drug combination screen of targeted small molecule inhibitors in cancer cell lines.Scientific data · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe irinotecan-induced phosphokinome changes in colorectal cancer (CRC) cells were used to guide the selection of targeted agents to be tested in combination with irinotecan.
methodsPhosphokinome profiling with peptide arrays of tumour samples from nude mice xenografted with HT29 cells and treated or not with an effective dose of irinotecan was used to identify signalling pathways activated by irinotecan treatment. Then, drugs targeting these pathways were combined in vitro with irinotecan to test potential synergistic effect. The interactions between these drug combinations were assessed by a dose matrix approach. Confirmation of the most potential combination has been confirmed in vivo in xenografted mice.
resultsIrinotecan induced in vivo the activation of AKT and MEK1 phosphorylation. The dose matrix approach showed that BKM120 (PI3K inhibitor) and MEK162 (MEK inhibitor) are synergistic in vitro and in vivo with a cytostatic and cytotoxic effect, while combination of BKM120 and irinotecan or MEK162 and irinotecan are only additive or even antagonistic. However, the triple combination of SN38, BKM120 and MEK162 showed a better synergistic effect that BKM120 and MEK162, indicating that the cells need to inhibit both AKT and ERK pathways to become more sensitive to irinotecan-based chemotherapies.
conclusionAnalysis of chemotherapy-induced phosphokinome changes helps to elucidate the mechanisms of drug resistance and to guide the selection of targets for combination therapies with synergistic activity.
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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.