Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F11%3A00371716" target="_blank" >RIV/68378050:_____/11:00371716 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1371/journal.pone.0021632" target="_blank" >http://dx.doi.org/10.1371/journal.pone.0021632</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0021632" target="_blank" >10.1371/journal.pone.0021632</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance

Popis výsledku v původním jazyce

Documented sensitivity of melanoma cells to PLX4720, a selective BRAFV600E inhibitor, is based on the presence of mutant BRAF(V600E) alone, while wt-BRAF or mutated KRAS result in cell proliferation. In colon cancer BRAF, like KRAS mutations, tend to co-exist with those in PIK3CA. Treatment of two genetically different BRAF(V600E) mutant colon cancer cell lines with BRAF(V600E)inhibitor PLX4720 conferred complete resistance to cell death and TRAIL,an apoptosis inducing agent, was used synergistically inorder to achieve cell death by apoptosis in RKO(BRAFV600E/PIK3CAH1047) cells. For the same level of apoptosis in HT29(BRAFV600E/PIK3CAP449T) cells, TRAIL was combined with 17-AAG, an Hsp90 inhibitor. Pharmacological suppression of the PI3K pathway further enhances the synergistic effect between TRAIL and PLX4720 in RKO cells, indicating the presence of PIK3CA(MT) as the inhibitory factor. Another rational combination includes 17-AAG synergism with TRAIL in a BRAF(V600E) mutant cells.

Název v anglickém jazyce

Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance

Popis výsledku anglicky

Documented sensitivity of melanoma cells to PLX4720, a selective BRAFV600E inhibitor, is based on the presence of mutant BRAF(V600E) alone, while wt-BRAF or mutated KRAS result in cell proliferation. In colon cancer BRAF, like KRAS mutations, tend to co-exist with those in PIK3CA. Treatment of two genetically different BRAF(V600E) mutant colon cancer cell lines with BRAF(V600E)inhibitor PLX4720 conferred complete resistance to cell death and TRAIL,an apoptosis inducing agent, was used synergistically inorder to achieve cell death by apoptosis in RKO(BRAFV600E/PIK3CAH1047) cells. For the same level of apoptosis in HT29(BRAFV600E/PIK3CAP449T) cells, TRAIL was combined with 17-AAG, an Hsp90 inhibitor. Pharmacological suppression of the PI3K pathway further enhances the synergistic effect between TRAIL and PLX4720 in RKO cells, indicating the presence of PIK3CA(MT) as the inhibitory factor. Another rational combination includes 17-AAG synergism with TRAIL in a BRAF(V600E) mutant cells.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

—

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

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

Název periodika

PLoS ONE

ISSN

1932-6203

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

19

Strana od-do

"e21632"

Kód UT WoS článku

000292092600065

EID výsledku v databázi Scopus

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