keyword
MENU ▼
Read by QxMD icon Read
search

Encorafenib

keyword
https://www.readbyqxmd.com/read/28724666/braf-inhibitors-amplify-the-proapoptotic-activity-of-mek-inhibitors-by-inducing-er-stress-in-nras-mutant-melanoma
#1
Heike Niessner, Tobias Sinnberg, Corinna Kosnopfel, Keiran S M Smalley, Daniela Beck, Christian Praetorius, Marion Mai, Stefan Beissert, Dagmar Kulms, Martin Schaller, Claus Garbe, Keith T Flaherty, Dana Westphal, Ines Wanke, Friedegund Meier
Purpose: NRAS mutations in malignant melanoma are associated with aggressive disease requiring rapid antitumor intervention, but there is no approved targeted therapy for this subset of patients. In clinical trials, the MEK inhibitor (MEKi) binimetinib displayed modest antitumor activity, making combinations a requisite. In a previous study, the BRAF inhibitor (BRAFi) vemurafenib was shown to induce endoplasmic reticulum (ER) stress that together with inhibition of the RAF-MEK-ERK (MAPK) pathway amplified its proapoptotic activity in BRAF-mutant melanoma...
July 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28640105/glomerulonephritis-and-granulomatous-vasculitis-in-kidney-as-a-complication-of-the-use-of-braf-and-mek-inhibitors-in-the-treatment-of-metastatic-melanoma-a-case-report
#2
Mehdi Maanaoui, Camille Saint-Jacques, Viviane Gnemmi, Marie Frimat, Arnaud Lionet, Marc Hazzan, Christian Noël, François Provot
RATIONALE: BRAF and MEK inhibitors have significantly improved the prognosis of metastatic melanoma, by inhibiting both the mitogen-activated protein kinase (MAP-kinase) pathway. They are associated with infrequent adverse kidney events. Most of these are related to the use of BRAF inhibitors and involve interstitial nephritis with acute tubular necrosis. PATIENT CONCERNS: We report a unique case of glomerulonephritis with renal granulomatous vasculitis in a patient diagnosed with metastatic melanoma treated with BRAF and MEK inhibitors...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28611198/phase-i-dose-escalation-and-expansion-study-of-the-braf-inhibitor-encorafenib-lgx818-in-metastatic-braf-mutant-melanoma
#3
Jean-Pierre Delord, Caroline Robert, Marta Nyakas, Grant A McArthur, Ragini Kudchakar, Amit Mahipal, Yasuhide Yamada, Ryan J Sullivan, Ana Arance, Richard F Kefford, Matteo S Carlino, Manuel Hidalgo, Carlos Gomez-Roca, Daniela Michel, Abdelkader Seroutou, Vassilios Aslanis, Giordano Caponigro, Darrin Stuart, Laure Moutouh-de Parseval, Tim Demuth, Reinhard Dummer
PURPOSE: Encorafenib, a selective BRAF-inhibitor (BRAFi), has a pharmacological profile that is distinct from that of other clinically active BRAFis. We evaluated encorafenib in a phase I study in patients with BRAFi treatment-naive and pretreated BRAF-mutant melanoma. EXPERIMENTAL DESIGN: The pharmacological activity of encorafenib was first characterized preclinically. Encorafenib monotherapy was then tested across a range of once-daily (QD; 50-700mg) or twice-daily (75-150mg) regimens in a phase I, open-label, dose-escalation and -expansion study in adult patients with histologically confirmed advanced/metastatic BRAF-mutant melanoma...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28537004/mek-inhibitors-in-the-treatment-of-metastatic-melanoma-and-solid-tumors
#4
REVIEW
Antonio M Grimaldi, Ester Simeone, Lucia Festino, Vito Vanella, Martina Strudel, Paolo A Ascierto
The mitogen-activated protein kinase (MAPK) cascade is an intracellular signaling pathway involved in the regulation of cellular proliferation and the survival of tumor cells. Several different mutations, involving BRAF or NRAS, exert an oncogenic effect by activating the MAPK pathway, resulting in an increase in cellular proliferation. These mutations have become targets for new therapeutic strategies in melanoma and other cancers. Selective MEK inhibitors have the ability to inhibit growth and induce cell death in BRAF- and NRAS-mutant melanoma cell lines...
May 23, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28363909/a-phase-ib-dose-escalation-study-of-encorafenib-and-cetuximab-with-or-without-alpelisib-in-metastatic-braf-mutant-colorectal-cancer
#5
Robin M J M van Geel, Josep Tabernero, Elena Elez, Johanna C Bendell, Anna Spreafico, Martin Schuler, Takayuki Yoshino, Jean-Pierre Delord, Yasuhide Yamada, Martijn P Lolkema, Jason E Faris, Ferry A L M Eskens, Sunil Sharma, Rona Yaeger, Heinz-Josef Lenz, Zev A Wainberg, Emin Avsar, Arkendu Chatterjee, Savina Jaeger, Eugene Tan, Kati Maharry, Tim Demuth, Jan H M Schellens
Preclinical evidence suggests that concomitant BRAF and EGFR inhibition leads to sustained suppression of MAPK signaling and suppressed tumor growth in BRAF(V600E) colorectal cancer models. Patients with refractory BRAF(V600)-mutant metastatic CRC (mCRC) were treated with a selective RAF kinase inhibitor (encorafenib) plus a monoclonal antibody targeting EGFR (cetuximab), with (n = 28) or without (n = 26) a PI3Kα inhibitor (alpelisib). The primary objective was to determine the maximum tolerated dose (MTD) or a recommended phase II dose...
June 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28277830/can-binimetinib-encorafenib-and-masitinib-be-more-efficacious-than-currently-available-mutation-based-targeted-therapies-for-melanoma-treatment
#6
REVIEW
Megan C Turner, Kara Rossfeld, April K S Salama, Douglas Tyler, Georgia Beasley
Historically, there were few effective and durable treatments for metastatic melanoma. Recently, mutation based targeted therapies have revolutionized treatment and outcomes for patients with metastatic melanoma. Specifically, inhibitors aimed at BRAF, NRAS, and C-KIT mutations are now commonly used in treatment for patients harboring the specific mutations. Areas covered: A brief review of current BRAF, NRAS, and C-KIT inhibitors provides background for a thorough review of newly developed agents namely binimetinib, a MEK inhibitor, encorafenib a BRAF inhibitor, and masitinib which inhibits C-KIT...
April 2017: Expert Opinion on Pharmacotherapy
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
#7
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
#8
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
#9
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
#10
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
#11
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
1
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"