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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elli Narvi, Katri Vaparanta, Anna Karrila, Deepankar Chakroborty, Sakari Knuutila, Arto Pulliainen, Maria Sundvall, Klaus Elenius
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Cetuximab Epidermal Growth Factor Receptor (EGFR) EGFR Down-regulation BRAF Mutation Status EGFR mAbs Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6509ba9e46f9450ab57d53a05d5f7f52
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6509ba9e46f9450ab57d53a05d5f7f52
record_format	dspace
spelling	oai:doaj.org-article:6509ba9e46f9450ab57d53a05d5f7f522021-12-02T15:08:17ZDifferent responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin10.1038/s41598-018-34938-y2045-2322https://doaj.org/article/6509ba9e46f9450ab57d53a05d5f7f522018-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34938-yhttps://doaj.org/toc/2045-2322Abstract 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.Elli NarviKatri VaparantaAnna KarrilaDeepankar ChakrobortySakari KnuutilaArto PulliainenMaria SundvallKlaus EleniusNature PortfolioarticleCetuximabEpidermal Growth Factor Receptor (EGFR)EGFR Down-regulationBRAF Mutation StatusEGFR mAbsMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cetuximab Epidermal Growth Factor Receptor (EGFR) EGFR Down-regulation BRAF Mutation Status EGFR mAbs Medicine R Science Q
spellingShingle	Cetuximab Epidermal Growth Factor Receptor (EGFR) EGFR Down-regulation BRAF Mutation Status EGFR mAbs Medicine R Science Q Elli Narvi Katri Vaparanta Anna Karrila Deepankar Chakroborty Sakari Knuutila Arto Pulliainen Maria Sundvall Klaus Elenius Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin
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.
format	article
author	Elli Narvi Katri Vaparanta Anna Karrila Deepankar Chakroborty Sakari Knuutila Arto Pulliainen Maria Sundvall Klaus Elenius
author_facet	Elli Narvi Katri Vaparanta Anna Karrila Deepankar Chakroborty Sakari Knuutila Arto Pulliainen Maria Sundvall Klaus Elenius
author_sort	Elli Narvi
title	Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin
title_short	Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin
title_full	Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin
title_fullStr	Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin
title_full_unstemmed	Different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin
title_sort	different responses of colorectal cancer cells to alternative sequences of cetuximab and oxaliplatin
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6509ba9e46f9450ab57d53a05d5f7f52
work_keys_str_mv	AT ellinarvi differentresponsesofcolorectalcancercellstoalternativesequencesofcetuximabandoxaliplatin AT katrivaparanta differentresponsesofcolorectalcancercellstoalternativesequencesofcetuximabandoxaliplatin AT annakarrila differentresponsesofcolorectalcancercellstoalternativesequencesofcetuximabandoxaliplatin AT deepankarchakroborty differentresponsesofcolorectalcancercellstoalternativesequencesofcetuximabandoxaliplatin AT sakariknuutila differentresponsesofcolorectalcancercellstoalternativesequencesofcetuximabandoxaliplatin AT artopulliainen differentresponsesofcolorectalcancercellstoalternativesequencesofcetuximabandoxaliplatin AT mariasundvall differentresponsesofcolorectalcancercellstoalternativesequencesofcetuximabandoxaliplatin AT klauselenius differentresponsesofcolorectalcancercellstoalternativesequencesofcetuximabandoxaliplatin
_version_	1718388188864577536

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

Ejemplares similares