dc.contributor.author | Chrisochoidou, Y | |
dc.contributor.author | Roy, R | |
dc.contributor.author | Farahmand, P | |
dc.contributor.author | Gonzalez, G | |
dc.contributor.author | Doig, J | |
dc.contributor.author | Krasny, L | |
dc.contributor.author | Rimmer, EF | |
dc.contributor.author | Willis, AE | |
dc.contributor.author | MacFarlane, M | |
dc.contributor.author | Huang, PH | |
dc.contributor.author | Carragher, NO | |
dc.contributor.author | Munro, AF | |
dc.contributor.author | Murphy, DJ | |
dc.contributor.author | Veselkov, K | |
dc.contributor.author | Seckl, MJ | |
dc.contributor.author | Moffatt, MF | |
dc.contributor.author | Cookson, WOC | |
dc.contributor.author | Pardo, OE | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-02-06T09:42:42Z | |
dc.date.available | 2024-02-06T09:42:42Z | |
dc.date.issued | 2023-11-08 | |
dc.identifier | ARTN 725 | |
dc.identifier | 10.1038/s41419-023-06240-x | |
dc.identifier.citation | Cell Death and Disease, 2023, 14 (11), pp. 725 - | en_US |
dc.identifier.issn | 2041-4889 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6147 | |
dc.identifier.eissn | 2041-4889 | |
dc.identifier.eissn | 2041-4889 | |
dc.identifier.doi | 10.1038/s41419-023-06240-x | |
dc.identifier.doi | 10.1038/s41419-023-06240-x | |
dc.description.abstract | Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking. Here, using co-cultures of patient-derived mesothelioma cell lines and lung fibroblasts, we demonstrate that fibroblast activation is a self-propagated process producing a fibrotic extracellular matrix (ECM) and triggering drug resistance in mesothelioma cells. Following characterisation of mesothelioma cells/fibroblasts signalling crosstalk, we identify several FDA-approved targeted therapies as far more potent than standard-of-care Cisplatin/Pemetrexed in ECM-embedded co-culture spheroid models. In particular, the SRC family kinase inhibitor, Saracatinib, extends overall survival well beyond standard-of-care in a mesothelioma genetically-engineered mouse model. In short, we lay the foundation for the rational design of novel therapeutic strategies targeting mesothelioma/fibroblast communication for the treatment of mesothelioma patients. | |
dc.format | Electronic | |
dc.format.extent | 725 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | SPRINGERNATURE | en_US |
dc.relation.ispartof | Cell Death and Disease | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Animals | |
dc.subject | Mice | |
dc.subject | Humans | |
dc.subject | Mesothelioma, Malignant | |
dc.subject | Mesothelioma | |
dc.subject | Fibroblasts | |
dc.subject | Cancer-Associated Fibroblasts | |
dc.subject | Lung | |
dc.title | Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-10-20 | |
dc.date.updated | 2024-02-06T09:41:51Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1038/s41419-023-06240-x | en_US |
rioxxterms.licenseref.startdate | 2023-11-08 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37938546 | |
pubs.issue | 11 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular and Systems Oncology | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41419-023-06240-x | |
pubs.volume | 14 | |
icr.researchteam | Mol and Systems Oncology | en_US |
dc.contributor.icrauthor | Huang, Paul | |
icr.provenance | Deposited by Mr Arek Surman on 2024-02-06. Deposit type is initial. No. of files: 1. Files: Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.pdf | |