keyword
MENU ▼
Read by QxMD icon Read
search

Braf mek

keyword
https://www.readbyqxmd.com/read/27905182/optimizing-combination-dabrafenib-and-trametinib-therapy-in-braf-mutation-positive-advanced-melanoma-patients-guidelines-from-australian-melanoma-medical-oncologists
#1
Victoria Atkinson, Georgina V Long, Alexander M Menzies, Grant McArthur, Matteo S Carlino, Michael Millward, Rachel Roberts-Thomson, Benjamin Brady, Richard Kefford, Andrew Haydon, Jonathan Cebon
BRAF mutations occur commonly in metastatic melanomas and inhibition of mutant BRAF and the downstream kinase MEK results in rapid tumor regression and prolonged survival in patients. Combined therapy with BRAF and MEK inhibition improves response rate, progression free survival and overall survival compared with single agent BRAF inhibition, and reduces the skin toxicity that is seen with BRAF inhibitor monotherapy. However, this combination is associated with an increase in other toxicities, particularly drug-related pyrexia, which affects approximately 50% of patients treated with dabrafenib and trametinib (CombiDT)...
December 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27903124/diagnosis-and-management-of-craniopharyngiomas-in-the-era-of-genomics-and-targeted-therapy
#2
Juan Carlos Martinez-Gutierrez, Megan R D'Andrea, Daniel P Cahill, Sandro Santagata, Fred G Barker, Priscilla K Brastianos
Craniopharyngiomas are rare intracranial neoplasms that pose clinical challenges due to their location adjacent to vital structures. The authors have previously shown high mutation rates of BRAF V600E in papillary craniopharyngioma and of CTNNB1 in adamantinomatous craniopharyngioma. These activating driver mutations are potential therapeutic targets, and the authors have recently reported a significant response to BRAF/MEK inhibition in a patient with multiply recurrent PCP. As these targetable mutations warrant prospective research, the authors will be conducting a national National Cancer Institute-sponsored multicenter clinical trial to investigate BRAF/MEK inhibition in the treatment of craniopharyngioma...
December 2016: Neurosurgical Focus
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#3
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
November 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27893585/conjunctival-melanoma-responsive-to-combined-systemic-braf-mek-inhibitors
#4
Lora R Dagi Glass, Donald P Lawrence, Frederick A Jakobiec, Suzanne K Freitag
This report demonstrates a unique case of conjunctival melanoma harboring a BRAF V600E mutation responsive to systemic therapy with BRAF and MEK inhibitors. While systemic therapy would not be appropriate in patients with local disease alone, it may act therapeutically in cases of higher stage ocular surface and eyelid melanoma.
November 23, 2016: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/27892777/uveitis-and-papillitis-in-the-setting-of-dabrafenib-and-trametinib-therapy-for-metastatic-melanoma-a-case-report
#5
Jennifer Lim, Anna J Lomax, Catriona McNeil, Brian Harrisberg
PURPOSE: To report the diagnosis of acute VKH-like syndrome as a complication from dabrafenib (a serine/threonine inhibitor of BRAF V600) and trametinib (a MEK inhibitor). In combination, these targeted agents have been shown to prolong overall survival and progression free survival in BRAF mutant metastatic melanoma. METHODS: Retrospective medical chart review including radiologic and ophthalmologic investigations. RESULTS: A patient with metastatic melanoma being treated with dabrafenib and trametinib for 2 months presented with 1 week of visual blurring...
November 28, 2016: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/27885401/-cutaneous-side-effects-of-targeted-cancer-drugs
#6
REVIEW
J Below, B Homey, P A Gerber
In the past decades many new drugs were approved for the treatment of cancer and have been established as essential parts of various therapeutic regimens. In particular targeted therapies and immune checkpoint inhibitors that aim at specific carcinogenic signaling pathways or modulate the tumor-immune response have revolutionized cancer therapy. Despite their targeted actions, these drugs may lead to diverse adverse reactions. In particular, cutaneous toxicities represent a serious threat to patients' quality of life and may lead to dose reduction or therapy cessation...
November 24, 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/27863429/epigenetically-upregulated-wipf1-plays-a-major-role-in-braf-v600e-promoted-papillary-thyroid-cancer-aggressiveness
#7
Tao Zhang, Xiaopei Shen, Rengyun Liu, Guangwu Zhu, Justin Bishop, Mingzhao Xing
How the BRAF V600E mutation promotes the pathogenesis and aggressiveness of papillary thyroid cancer (PTC) is not completely understood. Here we explored a novel mechanism involving WASP interacting protein family member 1 (WIPF1). In PTC tumors, compared with the wild-type BRAF, BRAF V600E was associated with over-expression and hypomethylation of the WIPF1 gene. In thyroid cancer cell lines with wild-type BRAF, WIPF1 expression was robustly upregulated upon introduced expression of BRAF V600E (P=0.03) whereas the opposite was seen upon BRAF knockdown or treatment with BRAF V600E or MEK inhibitors in cells harboring BRAF V600E...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27848137/combined-braf-v600e-and-mek-blockade-for-braf-v600e-mutant-gliomas
#8
Jie Zhang, Tsun-Wen Yao, Rintaro Hashizume, Sujatmi Hariono, Krister J Barkovich, Qi-Wen Fan, Michael Prados, C David James, William A Weiss, Theodore Nicolaides
BRAF(V600E) is a common finding in glioma (about 10-60% depending on histopathologic subclassification). BRAF(V600E) monotherapy shows modest preclinical efficacy against BRAF(V600E) gliomas and also induces adverse secondary skin malignancies. Here, we examine the molecular mechanism of intrinsic resistance to BRAF(V600E) inhibition in glioma. Furthermore, we investigate BRAF(V600E)/MEK combination therapy that overcomes intrinsic resistance to BRAF(V600E) inhibitor and also prevents BRAF(V600E) inhibitor induced secondary malignancies...
November 15, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27846720/-molecular-mechanisms-of-carcinogenesis-of-epithelial-ovarian-cancers
#9
Z Müllerová, T Müller, K Křivánková, B Vojtěšek, P Müller
BACKGROUND: Epithelial ovarian carcinomas are one of the most common causes of death among gynecologic malignancies in the Czech population. This group of tumors is characterized by considerable heterogeneity in terms of its pathogenesis and response to therapy. It is questionable whether advances in the elucidation of molecular pathogenesis of various types of epithelial ovarian carcinomas can contribute to application of personalized targeted therapy. AIMS: This work aims to summarize current knowledge on carcinogenesis and molecular basis of epithelial ovarian cancers and point out their potential applications in clinical practice...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27846054/sequencing-treatment-in-brafv600-mutant-melanoma-anti-pd-1-before-and-after-braf-inhibition
#10
Douglas B Johnson, Eirini Pectasides, Emily Feld, Fei Ye, Shilin Zhao, Romany Johnpulle, Ryan Merritt, David F McDermott, Igor Puzanov, Donald Lawrence, Jeffrey A Sosman, Elizabeth Buchbinder, Ryan J Sullivan
Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAF-mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAF-mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58)...
November 14, 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27836854/a-novel-spectroscopically-determined-pharmacodynamic-biomarker-for-skin-toxicity-in-cancer-patients-treated-with-targeted-agents
#11
Antoine Azan, Peter J Caspers, Tom C Bakker Schut, Séverine Roy, Céline Boutros, Christine Mateus, Emilie Routier, Benjamin Besse, David Planchard, Atmane Seck, Nyam Kamsu-Kom, Gorana Tomasic, Senada Koljenović, Vincent Noordhoek Hegt, Texier Matthieu, Emilie Lanoy, Alexander M Eggermont, Angelo Paci, Caroline Robert, Gerwin J Puppels, Lluis M Mir
Raman spectroscopy is a non-invasive and label-free optical technique that provides detailed information about the molecular composition of a sample. In this study, we evaluated the potential of Raman spectroscopy to predict skin toxicity due to tyrosine-kinase inhibitors treatment. We acquired Raman spectra of skin of patients undergoing treatment with MEK, EGFR or BRAF inhibitors which are known to induce severe skin toxicity; for this pilot study, three patients were included for each inhibitor. Our algorithm, based on Partial Least Squares-Discriminant Analysis (PLS-DA) and cross-validation by bootstrapping, discriminated to variable degrees spectra from patient suffering and not suffering cutaneous adverse events...
November 11, 2016: Cancer Research
https://www.readbyqxmd.com/read/27816338/-adult-langerhans-cell-histiocytosis
#12
Mathilde de Menthon, Véronique Meignin, Alfred Mahr, Abdellatif Tazi
Langerhans cell histiocytosis (LCH) is a rare disease affecting both genders and can occur at any age. It often evolves through successive flares, and its severity varies from benign forms that don't require treatment to life threatening disease. Some patients have important functional impairment with psychological and social consequences and prolonged disability. LCH may affect only one organ, with uni- or multifocal involvement or be multisystem disease involving multiple organs. The organs most frequently involved are bones, lung, skin and the endocrinal system...
November 2, 2016: La Presse Médicale
https://www.readbyqxmd.com/read/27813079/the-plasma-membrane-ca-2-pump-pmca4b-inhibits-the-migratory-and-metastatic-activity-of-braf-mutant-melanoma-cells
#13
L Hegedus, T Garay, E Molnar, K Varga, A Bilecz, S Torok, R Padanyi, K Paszty, M Wolf, M Grusch, E Kallay, B Dome, W Berger, B Hegedus, A Enyedi
Oncogenic mutations of BRAF lead to constitutive ERK activity that supports melanoma cell growth and survival. While Ca(2+) signaling is a well-known regulator of tumor progression, the crosstalk between Ca(2+) signaling and the Ras-BRAF-MEK-ERK pathway is much less explored. Here we show that in BRAF mutant melanoma cells the abundance of the plasma membrane Ca(2+) ATPase isoform 4b (PMCA4b, ATP2B4) is low at baseline but markedly elevated by treatment with the mutant BRAF specific inhibitor vemurafenib. In line with these findings gene expression microarray data also shows decreased PMCA4b expression in cutaneous melanoma when compared to benign nevi...
November 4, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27810072/a-new-nfia-raf1-fusion-activating-the-mapk-pathway-in-pilocytic-astrocytoma
#14
Christina Westmose Yde, Astrid Sehested, Àngels Mateu-Regué, Olga Østrup, David Scheie, Karsten Nysom, Finn Cilius Nielsen, Maria Rossing
Pilocytic astrocytoma (PA) is one of the most common brain cancers among children and activation of the Mitogen-Activated Protein Kinase (MAPK) pathway is considered the hallmark. In the majority of cases, oncogenic BRAF fusions or BRAF V600E mutations are observed, while RAF1 or NF1 alterations are more rarely found. However, in some cases, no apparent cancer driver events can be identified. Here, we describe a novel fusion between the transcription factor nuclear factor 1A (NFIA) and Raf-1 proto-oncogene (RAF1) in a 5-year old boy with PA...
October 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27799065/a-case-study-of-an-integrative-genomic-and-experimental-therapeutic-approach-for-rare-tumors-identification-of-vulnerabilities-in-a-pediatric-poorly-differentiated-carcinoma
#15
Filemon S Dela Cruz, Daniel Diolaiti, Andrew T Turk, Allison R Rainey, Alberto Ambesi-Impiombato, Stuart J Andrews, Mahesh M Mansukhani, Peter L Nagy, Mariano J Alvarez, Andrea Califano, Farhad Forouhar, Beata Modzelewski, Chelsey M Mitchell, Darrell J Yamashiro, Lianna J Marks, Julia L Glade Bender, Andrew L Kung
BACKGROUND: Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case and molecular characterization of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given the rarity and poor prognosis associated with PDC in children, we utilized genomic analysis and preclinical models to validate oncogenic drivers and identify molecular vulnerabilities...
October 31, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27797976/genomic-heterogeneity-and-exceptional-response-to-dual-pathway-inhibition-in-anaplastic-thyroid-cancer
#16
William J Gibson, Daniel T Ruan, Vera A Paulson, Justine A Barletta, Glenn J Hanna, Stefan Kraft, Antonio Calles, Matthew A Nehs, Francis D Moore, Amaro Taylor-Weiner, Jeremiah A Wala, Travis I Zack, Thomas C Lee, Fiona M Fennessy, Erik K Alexander, Tom Tomas, Pasi A Janne, Levi A Garraway, Scott L Carter, Rameen Beroukhim, Jochen H Lorch, Eliezer Van Allen
PURPOSE: Cancers may resist single-agent targeted therapies when the flux of cellular growth signals is shifted from one pathway to another. Blockade of multiple pathways may be necessary for effective inhibition of tumor growth. We document a case in which a patient with anaplastic thyroid carcinoma (ATC) failed to respond to either mTOR or combined RAF/MEK inhibition, but experienced a dramatic response when both drug regimens were combined. EXPERIMENTAL DESIGN: Multi-region whole-exome sequencing of five diagnostic and four autopsy tumor biopsies was performed...
October 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27792246/inhibition-of-histone-deacetylases-in-melanoma-a-perspective-from-bench-to-bedside
#17
REVIEW
Eva Hornig, Markus V Heppt, Saskia A Graf, Thomas Ruzicka, Carola Berking
Histone deacetylases (HDACs) are critically involved in epigenetic gene regulation through alterations of the chromatin status of DNA. Aberrant expression, dysregulation of their enzymatic activity or imbalances between HDACs and histone acetyltransferases are likely involved in the development and progression of cancer. Pharmacologic inhibition of HDACs shows potent antitumor activity in a panel of malignancies such as colon or gastric cancer and multiple myeloma. In this review, we summarize the current knowledge of HDACs in melanoma and evaluate the application of HDAC inhibition from an experimental and clinical perspective...
November 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27791198/co-existence-of-braf-and-nras-driver-mutations-in-the-same-melanoma-cells-results-in-heterogeneity-of-targeted-therapy-resistance
#18
Marieke I G Raaijmakers, Daniel S Widmer, Apurva Narechania, Ossia Eichhoff, Sandra N Freiberger, Judith Wenzina, Phil F Cheng, Daniela Mihic-Probst, Rob Desalle, Reinhard Dummer, Mitchell P Levesque
Acquired chemotherapeutic resistance of cancer cells can result from a Darwinistic evolution process in which heterogeneity plays an important role. In order to understand the impact of genetic heterogeneity on acquired resistance and second line therapy selection in metastatic melanoma, we sequenced the exomes of 27 lesions which were collected from 3 metastatic melanoma patients treated with targeted or non-targeted inhibitors. Furthermore, we tested the impact of a second NRAS mutation in 7 BRAF inhibitor resistant early passage cell cultures on the selection of second line therapies...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27790118/two-case-reports-of-rare-braf-mutations-in-exon-11-and-exon-15-with-discussion-of-potential-treatment-options
#19
Georg Richtig, Ariane Aigelsreiter, Karl Kashofer, Emina Talakic, Romana Kupsa, Helmut Schaider, Erika Richtig
BRAF mutations occur in up to 50% of melanomas. Mutations in the BRAF gene directly influence the patient's treatment because several inhibitors are available that only target BRAF(V600) mutations. Herein, we describe two cases of patients with metastatic melanomas, each carrying a 'nonstandard' mutation in the BRAF gene: BRAF(K601E) and BRAF(G466E), respectively. The first patient was treated with a MEK inhibitor and the second one with ipilimumab. However, not all BRAF mutations result in increased BRAF kinase activity, and clinical data for 'nonstandard' mutations, such as those described in our case report, are sparse...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/27787543/systemic-therapy-for-previously-untreated-advanced-braf-mutated-melanoma-a-systematic-review-and-network-meta-analysis-of-randomized-clinical-trials
#20
Tahira Devji, Oren Levine, Binod Neupane, Joseph Beyene, Feng Xie
Importance: Multiple effective first-line systemic treatment options are available for patients with advanced BRAF-mutated melanoma. A lack of head-to-head randomized clinical trials (RCTs) comparing targeted and immunotherapies leaves uncertainty regarding optimal first-line treatment. Objective: To estimate the relative efficacy and safety of systemic therapies for advanced, treatment-naive, BRAF-mutated melanoma. Data Sources: We searched MEDLINE, Embase, and the Cochrane Central Registry of Controlled Trials for phase 2 or 3 RCTs published up until April 29, 2016...
October 27, 2016: JAMA Oncology
keyword
keyword
84596
1
2
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"