ArticleBritish journal of cancer2010
Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer.
Article in British journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00499486 (Phase II Clinical, Biological and Pharmacological Study of Rapamycin), which is not on this map. Cited by 46 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.
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.
Phase II Clinical, Biological and Pharmacological Study of Rapamycin (Rapamune®, Sirolimus) in Patients With Advanced Pancreatic Cancer
Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
- Gemcitabine Combined with the mTOR Inhibitor Temsirolimus in Patients with Locally Advanced or Metastatic Pancreatic Cancer. A Hellenic Cooperative Oncology Group Phase I/II Study.Targeted oncology · 2018Trial
- Extracellular vesicle-mediated gene therapy targets BRAFJournal of nanobiotechnology · 2025Article
- Inhibitory effects of the combination of rapamycin with gemcitabine plus paclitaxel on the growth of pancreatic cancer tumors.Human cell · 2025Article
- Patient-Derived-Xenografts in Mice: A Preclinical Platform for Cancer Research.Cold Spring Harbor perspectives in medicine · 2024Review
- Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer.International journal of molecular sciences · 2024Review
- Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor?Therapeutic advances in medical oncology · 2024Review
- Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects.International journal of molecular sciences · 2022Review
- Elevated expression of nuclear receptor-binding SET domain 3 promotes pancreatic cancer cell growth.Cell death & disease · 2021Article
- Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy Studies.Cancers · 2021Review
- Molecular and Phenotypic Profiling for Precision Medicine in Pancreatic Cancer: Current Advances and Future Perspectives.Frontiers in oncology · 2021Review
- Polo-like kinase 1 is involved in apoptosis, invasion, and metastasis of pancreatic ductal adenocarcinoma.Translational cancer research · 2020Article
- Generation and application of patient-derived xenograft models in pancreatic cancer research.Chinese medical journal · 2019Review
- Clinical Implementation of Precision Medicine in Gastric Cancer.Journal of gastric cancer · 2019Review
- Targeting the complexity of Src signalling in the tumour microenvironment of pancreatic cancer: from mechanism to therapy.The FEBS journal · 2019Review
- Review
- MTOR inhibitor-based combination therapies for pancreatic cancer.British journal of cancer · 2018Article
- Metformin synergizes with rapamycin to inhibit the growth of pancreatic cancerOncology letters · 2018Article
- The Generation and Application of Patient-Derived Xenograft Model for Cancer Research.Cancer research and treatment · 2018Review
- Article
- Patient-derived xenografts effectively capture responses to oncology therapy in a heterogeneous cohort of patients with solid tumors.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe purpose of this work was to determine the efficacy of inhibiting mammalian target of rapamycin (mTOR) in pancreatic cancer preclinical models and translate preclinical observations to the clinic.
methodsTemsirolimus (20 mg Kg(-1) daily) was administered to freshly generated pancreatic cancer xenografts. Tumour growth inhibition was determined after 28 days. Xenografts were characterised at baseline by gene expression and comparative genomic hybridisation. Patients with advanced, gemcitabine-resistant pancreatic cancer were treated with sirolimus (5 mg daily). The primary end point was 6-month survival rate (6mSR). Correlative studies included immunohistochemistry assessment of pathway expression in baseline tumours, drug pharmacokinetics (PKs), response assessment by FDG-PET and pharmacodynamic effects in peripheral-blood mononuclear cells (PBMCs).
resultsIn all, 4 of 17 xenografts (23%) responded to treatment. Sensitive tumours were characterised by gene copy number variations and overexpression of genes leading to activation of the PI3K/Akt/mTOR pathway. Activation of p70S6K correlated with drug activity in the preclinical studies. Sirolimus was well tolerated in the clinic, showed predictable PKs, exerted pathway inhibition in post-treatment PBMCs and resulted in a 6mSR of 26%. No correlation, however, was found between activated p70S6K in tumour tissues and anti-tumour effects.
conclusionSirolimus activity in pancreatic cancer was marginal and not predicted by the selected biomarker.
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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.