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dc.contributor.authorSchenk, Maximilian W.
dc.contributor.authorHumphrey, Sam
dc.contributor.authorHossain, AS Md Mukarram
dc.contributor.authorRevill, Mitchell
dc.contributor.authorPearsall, Sarah
dc.contributor.authorLallo, Alice
dc.contributor.authorBrown, Stewart
dc.contributor.authorBratt, Samuel
dc.contributor.authorGalvin, Melanie
dc.contributor.authorDescamps, Tine
dc.contributor.authorZhou, Cong
dc.contributor.authorPearce, Simon P
dc.contributor.authorPriest, Lynsey
dc.contributor.authorGreenhalgh, Michelle
dc.contributor.authorChaturvedi, Anshuman
dc.contributor.authorKerr, Alastair
dc.contributor.authorBlackhall, Fiona H
dc.contributor.authorDive, Caroline
dc.contributor.authorFrese, Kristopher K.
dc.date.accessioned2022-01-11T12:00:00Z
dc.date.available2022-01-11T12:00:00Z
dc.date.issued2021en
dc.identifier.citationSchenk MW, Humphrey S, Hossain ASMM, Revill M, Pearsall S, Lallo A, et al. Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer Vol. 12, Nature Communications. Springer Science and Business Media LLC; 2021.en
dc.identifier.pmid34789728en
dc.identifier.doi10.1038/s41467-021-26823-6en
dc.identifier.urihttp://hdl.handle.net/10541/624936
dc.description.abstractSmall cell lung cancer (SCLC) has a 5-year survival rate of <7%. Rapid emergence of acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. Soluble guanylate cyclase (sGC) is recurrently upregulated in post-chemotherapy progression CDX models, which correlates with acquired chemoresistance. Expression and activation of sGC is regulated by Notch and nitric oxide (NO) signalling with downstream activation of protein kinase G. Genetic targeting of sGC or pharmacological inhibition of NO synthase re-sensitizes a chemoresistant CDX progression model in vivo, revealing this pathway as a mediator of chemoresistance and potential vulnerability of relapsed SCLC.en
dc.titleSoluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung canceren
dc.typeArticleen
dc.contributor.departmentCancer Research UK Manchester Institute Cancer Biomarker Centre, University of Manchester, Alderley Park, Macclesfield, SK10 4TG,en
dc.identifier.journalNature Communicationsen
dc.description.noteen]
refterms.dateFOA2022-04-12T08:08:11Z


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