Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin

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dc.contributor.author Narvi, Elli
dc.contributor.author Vaparanta, Katri
dc.contributor.author Karrila, Anna
dc.contributor.author Chakroborty, Deepankar
dc.contributor.author Knuutila, Sakari
dc.contributor.author Pulliainen, Arto
dc.contributor.author Sundvall, Maria
dc.contributor.author Elenius, Klaus
dc.date.accessioned 2018-12-18T08:50:02Z
dc.date.available 2018-12-18T08:50:02Z
dc.date.issued 2018-11-08
dc.identifier.citation Narvi , E , Vaparanta , K , Karrila , A , Chakroborty , D , Knuutila , S , Pulliainen , A , Sundvall , M & Elenius , K 2018 , ' Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin ' , Scientific Reports , vol. 8 , 16579 . https://doi.org/10.1038/s41598-018-34938-y
dc.identifier.other PURE: 120253940
dc.identifier.other PURE UUID: 81ad5f99-9cd5-435d-bdb0-064c47112da2
dc.identifier.other WOS: 000449499500068
dc.identifier.other Scopus: 85056253602
dc.identifier.uri http://hdl.handle.net/10138/277463
dc.description.abstract Therapeutic protocols including EGFR antibodies in the context of oxaliplatin-based regimens have variable clinical effect in colorectal cancer. Here, we tested the effect of the EGFR antibody cetuximab in different sequential combinations with oxaliplatin on the growth of colorectal cancer cells in vitro and in vivo. Cetuximab reduced the efficacy of oxaliplatin when administered before oxaliplatin but provided additive effect when administered after oxaliplatin regardless of the KRAS or BRAF mutation status of the cells. Systemic gene expression and protein phosphorylation screens revealed alternatively activated pathways regulating apoptosis, cell cycle and DNA damage response. Functional assays indicated that cetuximab-induced arrest of the cells into the G1 phase of the cell cycle was associated with reduced responsiveness of the cells to subsequent treatment with oxaliplatin. In contrast, oxaliplatin-enhanced responsiveness to subsequent treatment with cetuximab was associated with increased apoptosis, inhibition of STAT3 activity and increased EGFR down-regulation. This preclinical study indicates that optimizing the sequence of administration may enhance the antitumor effect of combination therapy with EGFR antibodies and oxaliplatin. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject INHIBITORS
dc.subject STAT3
dc.subject COMBINATION
dc.subject GEFITINIB
dc.subject THERAPY
dc.subject ACTIVATION
dc.subject RESISTANCE
dc.subject APOPTOSIS
dc.subject 3111 Biomedicine
dc.subject 3122 Cancers
dc.title Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin en
dc.type Article
dc.contributor.organization Medicum
dc.contributor.organization Department of Pathology
dc.contributor.organization University of Helsinki
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41598-018-34938-y
dc.relation.issn 2045-2322
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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