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https://www.readbyqxmd.com/read/28329154/brugada-syndrome-induced-by-braf-and-mek-inhibitors-in-a-melanoma-patient
#1
Charlée Nardin, Morgane Colas, Marc Badoz, Blandine Roche-Kubler, Nicolas Meneveau, Eve Puzenat, François Aubin
No abstract text is available yet for this article.
March 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28325255/mucosal-melanoma-of-the-head-and-neck
#2
REVIEW
Paolo Antonio Ascierto, Remo Accorona, Gerardo Botti, Davide Farina, Piero Fossati, Gemma Gatta, Helen Gogas, Davide Lombardi, Roberto Maroldi, Piero Nicolai, Marco Ravanelli, Vito Vanella
Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323504/pembrolizumab-use-for-the-treatment-of-advanced-melanoma
#3
Pol Specenier
Until recently, overall long term survival in patients with stage IV melanoma was lower than 10 %. However, the treatment of melanoma has evolved rapidly over the last few years, with the advent of inhibitors of BRAF and MEK and of immunotherapeutic agents including ipilimumab, nivolumab, and pembrolizumab. Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma...
March 21, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28320730/prediction-of-the-transporter-mediated-drug-drug-interaction-potential-of-dabrafenib-and-its-major-circulating-metabolites
#4
Harma Ellens, Marta Johnson, Sarah K Lawrence, Cory A Watson, Liangfu Chen, Lauren E Richards-Peterson
The BRAF inhibitor dabrafenib was recently approved for the treatment of certain BRAF V600 mutation-positive tumors, either alone or in combination therapy with the MEK inhibitor trametinib. This article presents the dabrafenib transporter-mediated drug-drug interaction risk assessment, which is currently an important part of drug development, regulatory submission and drug registration. Dabrafenib and its major circulating metabolites (hydroxy-, carboxy- and desmethyl-dabrafenib) were investigated as inhibitors of the clinically relevant transporters Pgp, BCRP, OATP1B1, OATP1B3, OCT2, OAT1 and OAT3...
March 20, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28314720/rechallenge-with-braf-and-mek-inhibitors-has-antitumor-activity
#5
(no author information available yet)
Resistance to BRAF plus MEK inhibitors may be reversible in patients with BRAF(V600)-mutant melanoma.
March 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28299583/braf-plus-mek-targeted-drugs-a-new-standard-of-treatment-for-braf-mutant-advanced-melanoma
#6
Paola Queirolo, Francesco Spagnolo
BRAF plus MEK-targeted drugs have out-performed BRAF inhibitor monotherapy in three randomized phase 3 studies, and such combinations have become a new standard of treatment for BRAF-mutant advanced melanoma. With an overall response rate of about 70%, no other therapy in melanoma has shown a better response rate in late-phase clinical trials than combined BRAF and MEK inhibitors; the rapid kinetics of response make them the ideal front-line treatment for symptomatic, BRAF-mutant advanced melanoma patients...
March 15, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28299358/a-novel-potentially-targetable-tmem106b-braf-fusion-in-pleomorphic-xanthoastrocytoma
#7
Susan J Hsiao, Matthias A Karajannis, Daniel Diolaiti, Mahesh M Mansukhani, Julia Glade Bender, Andrew L Kung, James H Garvin
Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization (WHO) Grade II glioma occurring primarily in children and young adults. Most PXAs harbor the known activating mutation BRAF V600E. We report a case of locally recurrent PXA with anaplastic features in a 10-yr-old female. The PXA was negative by immunohistochemical (IHC) staining for BRAF V600E mutation. Whole-exome and transcriptome sequencing of the tumor confirmed the absence of BRAF V600E, but identified copy-number alterations (including loss of the tumor suppressor CDKN2A) and a novel TMEM106B-BRAF fusion...
March 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28297625/genomics-of-hairy-cell-leukemia
#8
Enrico Tiacci, Valentina Pettirossi, Gianluca Schiavoni, Brunangelo Falini
Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior...
March 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28282860/strategies-for-overcoming-resistance-in-tumours-harboring-braf-mutations
#9
REVIEW
Nourah Mohammad Obaid, Karen Bedard, Weei-Yuarn Huang
The development of resistance to previously effective treatments has been a challenge for health care providers and a fear for patients undergoing cancer therapy. This is an unfortunately frequent occurrence for patients undergoing targeted therapy for tumours harboring the activating V600E mutation of the BRAF gene. Since the initial identification of the BRAF mutation in 2002, a series of small molecular inhibitors that target the BRAFV600E have been developed, but intrinsic and acquired resistance to these drugs has presented an ongoing challenge...
March 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28281325/b-raf-mutations-are-associated-with-increased-iron-regulatory-protein-2-expression-in-colorectal-tumourigenesis
#10
Richard D Horniblow, Matthew Bedford, Robert Hollingworth, Sarah Evans, Emily Sutton, Neeraj Lal, Andrew Beggs, Tariq H Iqbal, Chris Tselepis
A role for iron in carcinogenesis is supported by evidence that iron metabolism proteins are modulated in cancer progression. To date however, the expression of IRP2 (Iron Regulatory Protein-2), which is known to regulate several iron metabolism proteins, has not been assessed in colorectal cancer. Expression of IRP2 was assessed by qRT-PCR and immunohistochemistry in human colorectal cancer tissue. By interrogating The Cancer Genome Atlas (TCGA) database, expression of IRP2 and transferrin receptor-1 (TfR1) was assessed relative to common mutations that are known to occur in cancer...
March 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#11
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28278423/digoxin-plus-trametinib-therapy-achieves-disease-control-in-braf-wild-type-metastatic-melanoma-patients
#12
Arthur E Frankel, Ugur Eskiocak, Jennifer G Gill, Stacy Yuan, Vijayashree Ramesh, Thomas W Froehlich, Chul Ahn, Sean J Morrison
This is the first prospective study of a combination therapy involving a cardenolide and a MEK inhibitor for metastatic melanoma. Whereas BRAF mutant melanomas can exhibit profound responses to treatment with BRAF and MEK inhibitors, there are fewer options for BRAF wild-type melanomas. In preclinical studies, we discovered that cardenolides synergize with MEK inhibitor to promote the regression of patient-derived xenografts irrespective of BRAF mutation status. We therefore conducted a phase 1B study of digoxin 0...
March 6, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28278349/beyond-the-braf-v-600e-hotspot-biology-and-clinical-implications-of-rare-braf-gene-mutations-in-melanoma-patients
#13
REVIEW
G Richtig, C Hoeller, K Kashofer, A Aigelsreiter, A Heinemann, L N Kwong, M Pichler, E Richtig
BRAF mutations can be found in approximately 50% of melanomas, whereas the most common BRAF mutation is the substitution of a valine residue at codon 600 to glutamic acid. BRAF(V)(600E) occurs in up to 95% of all melanoma cases and can be successfully blocked by using a combination of BRAF- and MEK-inhibitors. Due to the wider availability of next-generation sequencing, more non-V600 BRAF mutations are emerging, and the clinical implications of these mutations are widely unknown. In this review, we will discuss the biology of the MAPK-pathway and its different types of BRAF mutations as well as their effect on MEK activation...
March 9, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28277830/can-binimetinib-encorafenib-and-masitinib-be-more-efficacious-than-currently-available-mutation-based-targeted-therapies-for-melanoma-treatment
#14
Megan 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...
March 3, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28277101/radiosurgery-stereotactic-radiotherapy-in-combination-with-immunotherapy-and-targeted-agents-for-melanoma-brain-metastases
#15
Elisabetta Trino, Cristina Mantovani, Serena Badellino, Umberto Ricardi, Andrea Riccardo Filippi
The clinical landscape of advanced melanoma drastically changed after the introduction of both targeted therapies and immunotherapy. This rapid development in systemic therapies led to a change in the management of patients with brain metastases, with the subsequent need to re-assess the role of local therapies, in particular stereotactic radiosurgery (SRS). Areas covered: In this non-systematic review, we report on the current knowledge on the use of SRS in combination with immunotherapy and BRAF/MEK inhibitors for patients with melanoma brain metastases, as well as ongoing trials in this field...
March 1, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28275910/mechanisms-of-drug-resistance-in-melanoma
#16
Matthew Winder, Amaya Virós
Metastatic melanoma is associated with poor outcome and is largely refractory to the historic standard of care. In recent years, the development of targeted small-molecule inhibitors and immunotherapy has revolutionised the care and improved the overall survival of these patients. Therapies targeting BRAF and MEK to block the mitogen-activated protein kinase (MAPK) pathway were the first to show unprecedented clinical responses. Following these encouraging results, antibodies targeting immune checkpoint inhibition molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD)-1, and PD-ligand1(PD-L1) demonstrated sustained tumour regression in a significant subset of patients by enabling an anti-tumour immunologic response...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28270557/raf1-braf-dimerization-integrates-the-signal-from-ras-to-erk-and-rok%C3%AE
#17
Andrea Varga, Karin Ehrenreiter, Bertram Aschenbrenner, Pawel Kocieniewski, Marek Kochanczyk, Tomasz Lipniacki, Manuela Baccarini
Downstream of growth factor receptors and of the guanine triphosphatase (GTPase) RAS, heterodimers of the serine/threonine kinases BRAF and RAF1 are critical upstream kinases and activators of the mitogen-activated protein kinase (MAPK) module containing the mitogen-activated and extracellular signal-regulated kinase kinase (MEK) and their targets, the extracellular signal-regulated kinase (ERK) family. Either direct or scaffold protein-mediated interactions among the components of the ERK module (the MAPKKKs BRAF and RAF1, MEK, and ERK) facilitate signal transmission...
March 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/28268065/a-second-chance-for-success-with-braf-and-mek-inhibitors-in-melanoma
#18
Kelly G Paulson, John A Thompson
No abstract text is available yet for this article.
March 3, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28268064/combination-of-dabrafenib-plus-trametinib-for-braf-and-mek-inhibitor-pretreated-patients-with-advanced-braf-v600-mutant-melanoma-an-open-label-single-arm-dual-centre-phase-2-clinical-trial
#19
Max Schreuer, Yanina Jansen, Simon Planken, Ines Chevolet, Teofila Seremet, Vibeke Kruse, Bart Neyns
BACKGROUND: Patients with BRAF(V600)-mutant melanoma benefit from treatment with the combination of BRAF and MEK inhibitors, but resistance and disease progression develops in most patients. Preclinical studies and case studies have indicated that acquired resistance to BRAF inhibition can be reversible. We aimed to assess the anti-tumour activity of rechallenge with BRAF plus MEK inhibition in a prospective clinical trial. METHODS: In this open-label, single arm, dual-centre, phase 2 academic study in Belgium, patients aged 18 years or older with BRAF(V600)-mutant melanoma who had previously progressed on BRAF inhibitors (with or without MEK inhibitors) and were off-treatment for at least 12 weeks, were treated with dabrafenib 150 mg orally twice per day plus trametinib 2 mg orally once per day...
March 3, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28264791/more-than-5000-patients-with-metastatic-melanoma-in-europe-per-year-do-not-have-access-to-recommended-first-line-innovative-treatments
#20
L Kandolf Sekulovic, K Peris, A Hauschild, A Stratigos, J-J Grob, P Nathan, R Dummer, A-M Forsea, C Hoeller, H Gogas, L Demidov, C Lebbe, C Blank, J Olah, L Bastholt, D Herceg, B Neyns, R Vieira, J Hansson, P Rutkowski, I Krajsova, M Bylaite-Bucinskiene, I Zalaudek, J Maric-Brozic, N Babovic, M Banjin, K Putnik, G Weinlich, V Todorovic, K Kirov, J Ocvirk, A Zhukavets, M Kukushkina, L De La Cruz Merino, A Ymeri, M Risteski, C Garbe
BACKGROUND: Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF)...
March 2, 2017: European Journal of Cancer
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