ArticleThe Journal of pathology2018
Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras-driven lung tumours.
Article in The Journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Hydrogel-embedded precision-cut lung slices support ex vivo culture of in vivo-induced premalignant lung lesions.Physiological reports · 2025Article
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- A Novel Method for Floxed Gene Manipulation Using TAT-Cre Recombinase in Ex Vivo Precision-Cut Lung Slices (PCLS).Bio-protocol · 2024Article
- Hydrogel-Embedded Precision-Cut Lung Slices Model Lung Cancer Premalignancy Ex Vivo.Advanced healthcare materials · 2024Article
- 3D cell culture models in research: applications to lung cancer pharmacology.Frontiers in pharmacology · 2024Review
- Development of Dual Diagnostic-Therapeutic Nanoformulation Effective Against Pancreatic Cancer in Animal Model.International journal of nanomedicine · 2024Article
- A method for TAT-Cre recombinase-mediated floxed allele modification in ex vivo tissue slices.Disease models & mechanisms · 2023Article
- Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services.Journal of personalized medicine · 2023Article
- Targeted therapy for rare lung cancers: Status, challenges, and prospects.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Precision Cut Lung Slices as a Preclinical Model for Non-Small Cell Lung Cancer Chemoprevention.Cancer prevention research (Philadelphia, Pa.) · 2023Article
- Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response.Antioxidants (Basel, Switzerland) · 2023Article
- Development of an adenosquamous carcinoma histopathology - selective lung metastasis model.Biology open · 2022Article
- Drug-induced tumor-specific cytotoxicity in a whole tissueFrontiers in oncology · 2022Article
- SOX9 has distinct roles in the formation and progression of different non-small cell lung cancer histotypes.The Journal of pathology · 2021Article
- Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments.Cell reports. Medicine · 2021Article
- Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery.American journal of respiratory cell and molecular biology · 2020Review
- Spa-RQ: an Image Analysis Tool to Visualise and Quantify Spatial Phenotypes Applied to Non-Small Cell Lung Cancer.Scientific reports · 2019Article
- Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma.Scientific reports · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision-cut slices from Kras-driven non-small-cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen-activated protein kinase (MAPK) activity in adenocarcinoma. In addition, high intertumour and intratumour variability was detected, particularly of MAPK and mammalian target of rapamycin (mTOR) complex 1 activity. Using short-term treatment of slice explants, we showed that cytotoxic responses to combination MAPK and phosphoinositide 3-kinase-mTOR inhibition correlate with the spatially defined activities of both pathways. Thus, whereas genetic drivers determine histopathology spectra, histopathology-associated and spatially variable signalling activities determine drug sensitivity. Our study is in support of spatial aspects of signalling heterogeneity being considered in clinical diagnostic settings, particularly to guide the selection of drug combinations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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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.