ArticleCancer chemotherapy and pharmacology2013
Synergistic interactions between sorafenib and everolimus in pancreatic cancer xenografts in mice.
Article in Cancer chemotherapy and pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric and Young Adult Solid Tumors.Pediatric blood & cancer · 2025Trial
- Practical Pharmacokinetic-Pharmacodynamic Models in Oncology.Pharmaceutics · 2025Review
- Mutant-Huntingtin Molecular Pathways Elucidate New Targets for Drug Repurposing.International journal of molecular sciences · 2023Review
- Targeting KRAS for the potential treatment of pancreatic ductal adenocarcinoma: Recent advancements provide hope (Review).Oncology reports · 2023Review
- A PK-PD model linking biomarker dynamics to progression-free survival in patients treated with everolimus and sorafenib combination therapy, EVESOR phase I trial.Cancer chemotherapy and pharmacology · 2023Article
- Clinical results of the EVESOR trial, a multiparameter phase I trial of everolimus and sorafenib combination in solid tumors.Cancer chemotherapy and pharmacology · 2023Article
- Dramatic response to targeted therapy in an aggressive olfactory neuroblastoma: illustrative case.Journal of neurosurgery. Case lessons · 2022Article
- Network controllability solutions for computational drug repurposing using genetic algorithms.Scientific reports · 2022Article
- A Novel Integrated Pharmacokinetic-Pharmacodynamic Model to Evaluate Combination Therapy and DetermineThe Journal of pharmacology and experimental therapeutics · 2021Article
- The Anti-Cancer Effects of a Zotarolimus and 5-Fluorouracil Combination Treatment on A549 Cell-Derived Tumors in BALB/c Nude Mice.International journal of molecular sciences · 2021Article
- Everolimus for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC).Expert opinion on investigational drugs · 2019Review
- Assessment of Three-Drug Combination Pharmacodynamic Interactions in Pancreatic Cancer Cells.The AAPS journal · 2018Article
- The efficacy of lapatinib and nilotinib in combination with radiation therapy in a model of NF2 associated peripheral schwannoma.Journal of neuro-oncology · 2017Article
- mTOR inhibitors in urinary bladder cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- FAK and paxillin, two potential targets in pancreatic cancer.Oncotarget · 2016Review
- Evaluation of in vivo responses of sorafenib therapy in a preclinical mouse model of PTEN-deficient of prostate cancer.Journal of translational medicine · 2015Article
- Prioritizing therapeutic targets using patient-derived xenograft models.Biochimica et biophysica acta · 2015Review
- Tiam1 siRNA enhanced the sensitivity of sorafenib on esophageal squamous cell carcinoma in vivo.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Personalising pancreas cancer treatment: When tissue is the issue.World journal of gastroenterology · 2014Review
- Pancreatic cancer.British journal of pharmacology · 2014Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMolecular targeting of cellular signaling pathways is a promising approach in cancer therapy, but often fails to achieve sustained benefit because of the activation of collateral cancer cell survival and proliferation pathways. We tested the hypothesis that a combination of targeted agents that inhibit compensatory pathways would be more effective than single agents in controlling pancreatic cancer cell growth. We investigated whether everolimus, an mTOR inhibitor, and sorafenib, a multi-kinase inhibitor, would together inhibit growth of low-passage, patient-derived pancreatic cancer xenografts in mice more efficaciously than either agent alone.
methodsTumor volume progression was measured following treatment with both drugs as single agents, in combination, and at multiple doses. Pharmacokinetics in tumors and other tissues was also assessed. Pharmacodynamic interactions were evaluated quantitatively.
resultsA 5-week regimen of daily oral doses of 10 mg/kg sorafenib and 0.5 mg/kg everolimus, alone and in combination, did not achieve significant tumor growth inhibition. Higher doses (20 mg/kg of sorafenib and 1 mg/kg of everolimus) inhibited tumor growth significantly when given alone and caused complete inhibition of growth when given in combination. Tumor volume progression was described by a linear growth model, and drug effects were described by Hill-type inhibition. Using population modeling approaches, dual-interaction parameter estimates indicated a highly synergistic pharmacodynamic interaction between the two drugs.
conclusionsThe results indicate that combinations of mTOR and multi-kinase inhibitors may offer greater efficacy in pancreatic cancer than either drug alone. Drug effects upon tumor stromal elements may contribute to the enhanced anti-tumor efficacy.
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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.