| |  Online-Ressource |
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| Verfasst von: | Närhi, Katja [VerfasserIn]  |
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| | Anders, Simon [VerfasserIn] |
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| Titel: | Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras-driven lung tumours |
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| Verf.angabe: | Katja Närhi, Ashwini S. Nagaraj, Elina Parri, Riku Turkki, Petra W. van Duijn, Annabrita Hemmes, Jenni Lahtela, Virva Uotinen, Mikko I. Mäyränpää, Kaisa Salmenkivi, Jari Räsänen, Nina Linder, Jan Trapman, Antti Rannikko, Olli Kallioniemi, Taija M. Af Hällström, Johan Lundin, Wolfgang Sommergruber, Simon Anders and Emmy W. Verschuren |
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| E-Jahr: | 2018 |
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| Jahr: | 2 April 2018 |
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| Umfang: | 13 S. |
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| Fussnoten: | Gesehen am 11.12.2019 |
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| Titel Quelle: | Enthalten in: The journal of pathology |
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| Ort Quelle: | Bognor Regis [u.a.] : Wiley, 1892 |
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| Jahr Quelle: | 2018 |
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| Band/Heft Quelle: | 245(2018), 1, Seite 101-113 |
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| ISSN Quelle: | 1096-9896 |
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| 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. |
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| DOI: | doi:10.1002/path.5059 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1002/path.5059 |
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| | Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/path.5059 |
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| | DOI: https://doi.org/10.1002/path.5059 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | non-small-cell lung cancer |
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| | oncogenic signalling |
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| | prostate cancer |
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| | spatial heterogeneity |
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| | targeted therapy |
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| | tissue slices |
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| K10plus-PPN: | 1685157556 |
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| Verknüpfungen: | → Zeitschrift |
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Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras-driven lung tumours / Närhi, Katja [VerfasserIn]; 2 April 2018 (Online-Ressource)
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