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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2019

Confidentiality

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

Name of the periodical

Mutagenesis

ISSN

0267-8357

e-ISSN

—

Volume of the periodical

34

Issue of the periodical within the volume

5-6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

403-411

UT code for WoS article

000509474200006

EID of the result in the Scopus database

2-s2.0-85077106490