Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR‐TKIs in non‐small cell lung cancer

Compensatory activation of the signal transduction pathways is one of the major obstacles for the targeted therapy of non‐small cell lung cancer (NSCLC). Herein, we present the therapeutic strategy of combined targeted therapy against the MEK and phosphoinositide‐3 kinase (PI3K) pathways for acquire...

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Veröffentlicht in:	Cancer science 2018-10, Vol.109 (10), p.3183-3196
Hauptverfasser:	Sato, Hiroki, Yamamoto, Hiromasa, Sakaguchi, Masakiyo, Shien, Kazuhiko, Tomida, Shuta, Shien, Tadahiko, Ikeda, Hirokuni, Hatono, Minami, Torigoe, Hidejiro, Namba, Kei, Yoshioka, Takahiro, Kurihara, Eisuke, Ogoshi, Yusuke, Takahashi, Yuta, Soh, Junichi, Toyooka, Shinichi
Format:	Artikel
Sprache:	eng
Schlagworte:	1-Phosphatidylinositol 3-kinase acquired resistance AKT protein Animals Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis c-Met protein Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - pathology Cell activation Cell growth Cell Line, Tumor Cell Proliferation - drug effects Clinical trials compensatory activation Drug resistance Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Drug Synergism Enzyme inhibitors Epidermal growth factor Epidermal growth factor receptors Epithelial-Mesenchymal Transition - drug effects ErbB Receptors - antagonists & inhibitors ErbB Receptors - genetics Extracellular signal-regulated kinase Feedback Female Humans Imidazoles - pharmacology Imidazoles - therapeutic use Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - pathology MAP kinase MEK inhibitor Mesenchyme Mice, Inbred BALB C Mice, Nude Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinase Kinases - metabolism Mutation Non-small cell lung carcinoma non‐small cell lung cancer Original Oxazepines - pharmacology Oxazepines - therapeutic use Phosphatidylinositol 3-Kinases - metabolism Phosphoinositide-3 Kinase Inhibitors Phosphorylation PI3K inhibitor Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Protein-tyrosine kinase Pyridones - pharmacology Pyridones - therapeutic use Pyrimidinones - pharmacology Pyrimidinones - therapeutic use Signal transduction Signal Transduction - drug effects Stem cells Tumors Xenograft Model Antitumor Assays
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