ArticlePloS one2013
Utilization of quantitative in vivo pharmacology approaches to assess combination effects of everolimus and irinotecan in mouse xenograft models of colorectal cancer.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 29 citations in OpenAlex.
- Rapamycin inhibits tamoxifen-induced endometrial proliferation in vitro as a pilot approach for endometrial protection in breast cancer.Scientific reports · 2025Article
- mTOR inhibitors as potential therapeutics for endometriosis: a narrative review.Molecular human reproduction · 2024Review
- Role of Gut Microbiota in Predisposition to Colon Cancer: A Narrative Review.Indian journal of microbiology · 2024Review
- HER3/Akt/mTOR pathway is a key therapeutic target for the reduction of triple‑negative breast cancer metastasis via the inhibition of CXCR4 expression.International journal of molecular medicine · 2023Article
- ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer.BMC cancer · 2022Article
- Mimicking and surpassing the xenograft model with cancer-on-chip technology.EBioMedicine · 2021Review
- The role of mouse models in colorectal cancer research-The need and the importance of the orthotopic models.Animal models and experimental medicine · 2020Review
- Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib.Investigational new drugs · 2019Article
- mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy.International journal of molecular sciences · 2019Review
- Everolimus Plus Ku0063794 Regimen Promotes Anticancer Effects against Hepatocellular Carcinoma Cells through the Paradoxical Inhibition of Autophagy.Cancer research and treatment · 2018Article
- Article
- Characterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1α axis inhibition.Oncotarget · 2017Article
- HSP90 inhibitor 17-DMAG exerts anticancer effects against gastric cancer cells principally by altering oxidant-antioxidant balance.Oncotarget · 2017Article
- Environmental influences in the etiology of colorectal cancer: the premise of metabolomics.Current pharmacology reports · 2017Article
- Assessment of non-linear combination effect terms for drug-drug interactions.Journal of pharmacokinetics and pharmacodynamics · 2016Review
- Antitumor activity of the aurora a selective kinase inhibitor, alisertib, against preclinical models of colorectal cancer.Oncotarget · 2016Article
- Molecular characterization of colorectal cancer patients and concomitant patient-derived tumor cell establishment.Oncotarget · 2016Article
- Comparative Metabolomic Profiling of Hepatocellular Carcinoma Cells Treated with Sorafenib Monotherapy vs. Sorafenib-Everolimus Combination Therapy.Medical science monitor : international medical journal of experimental and clinical research · 2015Article
- Combined inhibition of MEK and Aurora A kinase in KRAS/PIK3CA double-mutant colorectal cancer models.Frontiers in pharmacology · 2015Article
- Phospho-mTOR in non-tumour and tumour bladder urothelium: Pattern of expression and impact on urothelial bladder cancer patients.Oncology letters · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThe PI3K/AKT/mTOR pathway is frequently dysregulated in cancers and inhibition of mTOR has demonstrated the ability to modulate pro-survival pathways. As such, we sought to determine the ability of the mTOR inhibitor everolimus to potentiate the antitumor effects of irinotecan in colorectal cancer (CRC). EXPERIMENTAL
designThe combinatorial effects of everolimus and irinotecan were evaluated in vitro and in vivo in CRC cell lines harboring commonly found mutations in PIK3CA, KRAS and/or BRAF. Pharmacokinetically-directed dosing protocols of everolimus and irinotecan were established and used to assess the in vivo antitumor effects of the agents. At the end of treatment, 3-6 tumors per treatment arm were harvested for biomarker analysis by NMR metabolomics.
resultsEverolimus and irinotecan/SN38 demonstrated synergistic anti-proliferative effects in multiple CRC cell lines in vitro. Combination effects of everolimus and irinotecan were determined in CRC xenograft models using clinically-relevant dosing protocols. Everolimus demonstrated significant tumor growth inhibition alone and when combined with irinotecan in HT29 and HCT116 tumor xenografts. Metabolomic analysis showed that HT29 tumors were more metabolically responsive than HCT116 tumors. Everolimus caused a decrease in glycolysis in both tumor types whilst irinotecan treatment resulted in a profound accumulation of lipids in HT29 tumors indicating a cytotoxic effect.
conclusionsQuantitative analysis of tumor growth and metabolomic data showed that the combination of everolimus and irinotecan was more beneficial in the BRAF/PIK3CA mutant HT29 tumor xenografts, which had an additive effect, than the KRAS/PIK3CA mutant HCT116 tumor xenografts, which had a less than additive effect.
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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.