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Encorafenib

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https://www.readbyqxmd.com/read/27639128/liquid-chromatography-tandem-mass-spectrometric-assay-for-therapeutic-drug-monitoring-of-the-b-raf-inhibitor-encorafenib-the-egfr-inhibitors-afatinib-erlotinib-and-gefitinib-and-the-o-desmethyl-metabolites-of-erlotinib-and-gefitinib-in-human-plasma
#1
Rolf W Sparidans, Hilde Rosing, Johannes J M Rood, Jan H M Schellens, Jos H Beijnen
No abstract text is available yet for this article.
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27220786/-current-progress-and-feasibility-of-using-molecular-targeted-agent-combinations-for-metastatic-colorectal-cancer
#2
Toshiki Masuishi, Kei Muro
The efficacy of molecular-targeted agent combinations for the treatment of metastatic colorectal cancer has become increasingly evident over recent years, although none of these combinations have been recognized yet as a standard therapy. The intention here is to provide a synopsis of current progress in this developing area by reviewing existing publications and ongoing clinical trials. While bevacizumab plus anti-EGFR agents exhibit detrimental effects in first-line setting , a combination of bevacizumab with erlotinib has been suggested as an effective maintenance therapy...
April 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27116335/pyogenic-granuloma-in-patients-treated-with-selective-braf-inhibitors-another-manifestation-of-paradoxical-pathway-activation
#3
Benjamin Henning, Pascale Stieger, Jivko Kamarachev, Reinhard Dummer, Simone M Goldinger
Cutaneous toxicities under therapy with selective BRAF inhibitors such as vemurafenib or encorafenib (LGX818) are frequent, including plantar hyperkeratosis, squamous cell carcinoma, and second primary melanoma. Pyogenic granuloma is a benign, rapidly growing, eruptive hemangioma that often bleeds and ulcerates. Common causes are mechanical trauma and cast immobilization, as well as multiple drugs such as retinoids and antineoplastic agents. However, the development of pyogenic granuloma under treatment with encorafenib (LGX818) has not yet been reported...
June 2016: Melanoma Research
https://www.readbyqxmd.com/read/27028853/comparative-profiles-of-braf-inhibitors-the-paradox-index-as-a-predictor-of-clinical-toxicity
#4
Charles H Adelmann, Grace Ching, Lili Du, Rachael C Saporito, Varun Bansal, Lindy J Pence, Roger Liang, Woojin Lee, Kenneth Y Tsai
BRAF inhibitor (BRAFi) therapy is associated with the induction of neoplasia, most commonly cutaneous squamous cell carcinoma (cuSCC). This toxicity is explained in part by "paradoxical ERK activation," or the hyperactivation of ERK signaling by BRAFi in BRAF wild-type cells. However, the rate of cuSCC induction varies widely among BRAFi. To explore this mechanistically, we profiled paradoxical ERK activation by vemurafenib, dabrafenib, encorafenib (LGX818), and PLX8394, demonstrating that vemurafenib induces ERK activation the greatest, while dabrafenib and encorafenib have higher "paradox indices", defined as the pERK activation EC80 divided by the IC80 against A375, corresponding to wider therapeutic windows for achieving tumor inhibition without paradoxical ERK activation...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/26586345/encorafenib-lgx818-a-potent-braf-inhibitor-induces-senescence-accompanied-by-autophagy-in-brafv600e-melanoma-cells
#5
Zhen Li, Ke Jiang, Xiaofang Zhu, Guibin Lin, Fei Song, Yongfu Zhao, Yongjun Piao, Jiwei Liu, Wei Cheng, Xiaolin Bi, Peng Gong, Zhiqi Song, Songshu Meng
Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials. However, the underlying mechanism remains to be elucidated. Here we show that LGX818 potently decreased ERK phosphorylation and inhibited proliferation in BRAFV600E melanoma cell lines. Moreover, LGX818 downregulated CyclinD1 in a glycogen synthase kinase 3β-independent manner and induced cell cycle arrest in the G1 phase, Surprisingly, LGX818 triggered cellular senescence in BRAFV600E melanoma cells, as evidenced by increased β-galactosidase staining, while no appreciable induction of apoptosis was detected, as determined by Annexin V and propidium iodide staining and immunoblot analysis of caspase-3 processing and poly (ADP-ribose) polymerase cleavage...
January 28, 2016: Cancer Letters
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