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

• Published in: PloS one Vol. 6; no. 6; p. e21632
• Main Authors: Oikonomou, Eftychia, Koc, Michal, Sourkova, Vladimira, Andera, Ladislav, Pintzas, Alexander
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.06.2011; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenocarcinoma; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biology; Caco-2 Cells; Cancer; Cell death; Cell Line, Tumor; Cell proliferation; Class I Phosphatidylinositol 3-Kinases; Colon; Colon cancer; Colorectal cancer; Development and progression; Extracellular signal-regulated kinase; Flow Cytometry; Furans - pharmacology; Gene mutation; Health aspects; Heat shock proteins; Hsp90 protein; HT29 Cells; Humans; Immunoblotting; Immunoprecipitation; Indoles - pharmacology; Inhibitors; K-Ras protein; Kinases; MAP kinase; Medicine; MEK inhibitors; Melanoma; Microscopy, Fluorescence; Mutants; Mutation; Pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Pyridines - pharmacology; Pyrimidines - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Sulfonamides - pharmacology; Synergism; Synergistic effect; TNF-Related Apoptosis-Inducing Ligand - pharmacology; Tumor cell lines; Tumor necrosis factor-TNF; Tumors; Czech Republic

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 appearance of oncogenic alterations is complex , since BRAF, like KRAS mutations, te...