About: Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance     Goto   Sponge   NotDistinct   Permalink

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  • 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 in order 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.
  • 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 in order 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. (en)
Title
  • Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance
  • Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance (en)
skos:prefLabel
  • Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance
  • Selective BRAFV600E inhibitor PLX4720, requires TRAIL assistance to overcome oncogenic PIK3CA resistance (en)
skos:notation
  • RIV/68378050:_____/11:00371716!RIV12-AV0-68378050
http://linked.open...avai/riv/aktivita
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  • Z(AV0Z50520514)
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  • 6
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  • 228691
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  • RIV/68378050:_____/11:00371716
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  • 17-AAG; apoptosis; colorectal cancer (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [EA5294948BFE]
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  • PLoS ONE
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  • 6
http://linked.open...iv/tvurceVysledku
  • Anděra, Ladislav
  • Koc, Michal
  • Oikonomou, E.
  • Pintzas, A.
  • Šourková, Vladimíra
http://linked.open...ain/vavai/riv/wos
  • 000292092600065
http://linked.open...n/vavai/riv/zamer
issn
  • 1932-6203
number of pages
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  • 10.1371/journal.pone.0021632
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