KRAS pathway expression changes in pancreatic cancer models by conventional and experimental taxanes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00079152" target="_blank" >RIV/00023001:_____/19:00079152 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/19:43918493 RIV/00216208:11140/19:10395946 RIV/61989592:15110/19:73596751 RIV/75010330:_____/19:00012878

Výsledek na webu

<a href="https://academic.oup.com/mutage/article-abstract/34/5-6/403/5543279?redirectedFrom=fulltext" target="_blank" >https://academic.oup.com/mutage/article-abstract/34/5-6/403/5543279?redirectedFrom=fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/mutage/gez021" target="_blank" >10.1093/mutage/gez021</a>

Jazyk výsledku

angličtina

Název v původním jazyce

KRAS pathway expression changes in pancreatic cancer models by conventional and experimental taxanes

Popis výsledku v původním jazyce

The KRAS signalling pathway is pivotal for pancreatic ductal adenocarcinoma (PDAC) development. After the failure of most conventional cytotoxic and targeted therapeutics tested so far, the combination of taxane nab-paclitaxel (Abraxane) with gemcitabine recently demonstrated promising improvements in the survival of PDAC patients. This study aimed to explore interactions of conventional paclitaxel and experimental taxane SB-T-1216 with the KRAS signalling pathway expression in in vivo and in vitro PDAC models in order to decipher potential predictive biomarkers or targets for future individualised therapy. Mouse PDAC PaCa-44 xenograft model was used for evaluation of changes in transcript and protein levels of the KRAS signalling pathway caused by administration of experimental taxane SB-T-1216 in vivo. Subsequently, KRAS wild-type (BxPc-3) and mutated (MiaPaCa-2 and PaCa-44) cell line models were treated with paclitaxel to verify dysregulation of the KRAS signalling pathway gene expression profile in vitro and investigate the role of KRAS mutation status. By comparing the gene expression profiles, this study observed for the first time that in vitro cell models differ in the basal transcriptional profile of the KRAS signalling pathway, but there were no differences between KRAS mutated and wild-type cells in sensitivity to taxanes. Generally, the taxane administration caused a downregulation of the KRAS signalling pathway both in vitro and in vivo, but this effect was not dependent on the KRAS mutation status. In conclusion, putative biomarkers for prediction of taxane activity or targets for stimulation of taxane anticancer effects were not discovered by the KRAS signalling pathway profiling in various PDAC models.

Název v anglickém jazyce

KRAS pathway expression changes in pancreatic cancer models by conventional and experimental taxanes

Popis výsledku anglicky

The KRAS signalling pathway is pivotal for pancreatic ductal adenocarcinoma (PDAC) development. After the failure of most conventional cytotoxic and targeted therapeutics tested so far, the combination of taxane nab-paclitaxel (Abraxane) with gemcitabine recently demonstrated promising improvements in the survival of PDAC patients. This study aimed to explore interactions of conventional paclitaxel and experimental taxane SB-T-1216 with the KRAS signalling pathway expression in in vivo and in vitro PDAC models in order to decipher potential predictive biomarkers or targets for future individualised therapy. Mouse PDAC PaCa-44 xenograft model was used for evaluation of changes in transcript and protein levels of the KRAS signalling pathway caused by administration of experimental taxane SB-T-1216 in vivo. Subsequently, KRAS wild-type (BxPc-3) and mutated (MiaPaCa-2 and PaCa-44) cell line models were treated with paclitaxel to verify dysregulation of the KRAS signalling pathway gene expression profile in vitro and investigate the role of KRAS mutation status. By comparing the gene expression profiles, this study observed for the first time that in vitro cell models differ in the basal transcriptional profile of the KRAS signalling pathway, but there were no differences between KRAS mutated and wild-type cells in sensitivity to taxanes. Generally, the taxane administration caused a downregulation of the KRAS signalling pathway both in vitro and in vivo, but this effect was not dependent on the KRAS mutation status. In conclusion, putative biomarkers for prediction of taxane activity or targets for stimulation of taxane anticancer effects were not discovered by the KRAS signalling pathway profiling in various PDAC models.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Mutagenesis

ISSN

0267-8357

e-ISSN

—

Svazek periodika

34

Číslo periodika v rámci svazku

5-6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

403-411

Kód UT WoS článku

000509474200006

EID výsledku v databázi Scopus

2-s2.0-85077106490