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

The result's identifiers

  • Result code in 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>

  • Result on the web

    <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>

Alternative languages

  • Result language

    angličtina

  • Original language name

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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    EB - Genetics and molecular biology

  • OECD FORD branch

Result continuities

  • Project

  • Continuities

    Z - Vyzkumny zamer (s odkazem do CEZ)

Others

  • Publication year

    2011

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    PLoS ONE

  • ISSN

    1932-6203

  • e-ISSN

  • Volume of the periodical

    6

  • Issue of the periodical within the volume

    6

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    19

  • Pages from-to

    "e21632"

  • UT code for WoS article

    000292092600065

  • EID of the result in the Scopus database