keyword
MENU ▼
Read by QxMD icon Read
search

BRAF/MEK/ERK

keyword
https://www.readbyqxmd.com/read/29196297/acetylsalicylic-acid-governs-the-effect-of-sorafenib-in-ras-mutant-cancers
#1
Heinz Hammerlindl, Dinoop Ravindran Menon, Sabrina Hammerlindl, Abdullah Al Emran, Joachim Torrano, Katrin Sproesser, Divya Thakkar, Min Xiao, Victoria G Atkinson, Brian Gabrielli, Nikolas K Haass, Meenhard Herlyn, Clemens Krepler, Helmut Schaider
PURPOSE: Identify and characterize novel combinations of sorafenib with anti-inflammatory painkillers to target difficult to treat RAS-mutant cancer. EXPERIMENTAL DESIGN: The cytotoxicity of acetylsalicylic acid (aspirin) in combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in RAS-mutant cell lines in vitro. The underlying mechanism for the increased cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene knockdown...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29193645/mapk-inhibitors-induce-serine-peptidase-inhibitor-kazal-type-1-spink1-secretion-in-braf-v600e-mutant-colorectal-adenocarcinoma
#2
Kati Räsänen, Kien X Dang, Harri Mustonen, Tho H Ho, Susanna Lintula, Hannu Koistinen, Ulf-Håkan Stenman, Caj Haglund, Jakob Stenman
The mitogen-activated protein kinase (MAPK) pathway plays a central role in colorectal cancers (CRC). In particular, BRAF V600E-mutant tumors, which represent around 10% of CRCs, are refractory to current therapies. Over-expression and secretion of serine peptidase inhibitor Kazal type 1 (SPINK1) is observed in around 50% of CRCs and its serum level can be used as a biomarker for poor prognosis. Utilizing a recently developed Extendable Blocking Probe assay, we analyzed the BRAF mutation status in a CRC patient cohort (N=571) using tissue-derived RNA as the starting material...
November 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29180761/combined-inhibition-of-mek-and-nuclear-erk-translocation-has-synergistic-antitumor-activity-in-melanoma-cells
#3
Rand Arafeh, Karen Flores, Alona Keren-Paz, Galia Maik-Rachline, Naomi Gutkind, Steven Rosenberg, Rony Seger, Yardena Samuels
Genetic alterations in BRAF, NRAS and NF1 that activate the ERK cascade, account for over 80% of metastatic melanomas. However, ERK cascade inhibitors have been proven beneficial almost exclusively for BRAF mutant melanomas. One of the hallmarks of the ERK cascade is the nuclear translocation of ERK1/2, which is important mainly for the induction of proliferation. This translocation can be inhibited by the NTS-derived peptide (EPE) that blocks the ERK1/2-importin7 interaction, inhibits the nuclear translocation of ERK1/2, and arrests active ERK1/2 in the cytoplasm...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29171936/braf-internal-deletions-and-resistance-to-braf-mek-inhibitor-therapy
#4
Douglas B Johnson, Merrida A Childress, Zachary R Chalmers, Garrett M Frampton, Siraj M Ali, Samuel M Rubinstein, David Fabrizio, Jeffrey S Ross, Sohail Balasubramanian, Vincent A Miller, Philip J Stephens, Jeffrey A Sosman, Christine M Lovly
BRAF and MEK inhibitors have improved clinical outcomes in advanced, BRAFV600 - mutated melanomas. Acquired resistance occurs in most patients, with numerous and diverse drivers. We obtained pre-treatment and progression biopsies from a patient who progressed on dabrafenib and trametinib. In addition to a preserved BRAFV600E mutation, an internal deletion (rearrangement) of BRAF was observed in the progression sample. This deletion involved exons 2-8, which includes the Ras-binding domain, and is analogous to previously documented BRAF fusions and splice variants known to reactivate RAS-RAF-MEK-ERK signaling...
November 24, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29167314/wnt-%C3%AE-catenin-pathway-activation-mediates-adaptive-resistance-to-braf-inhibition-in-colorectal-cancer
#5
Guangming Chen, Chenxi Gao, Xuan Gao, Dennis Han Zhang, Shih-Fan Kuan, Timothy F Burns, Jing Hu
One of the most encouraging developments in oncology has been the success of BRAF inhibitors in BRAF-mutant melanoma. However, in contrast to its striking efficacy in BRAF-mutant melanomas, BRAF inhibitor monotherapy is ineffective in BRAF-mutant colorectal cancer (CRC). While many studies on BRAF inhibitor resistance in CRC have focused on mechanisms underlying the reactivation of the EGFR/RAS/RAF/MEK/ERK pathway, the current study focuses on identifying novel adaptive signaling mechanisms, a fresh angle on CRC resistance to BRAF inhibition...
November 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29107340/langerhans-cell-histiocytosis-a-neoplastic-disorder-driven-by-ras-erk-pathway-mutations
#6
REVIEW
Gary Tran, Thy N Huynh, Amy S Paller
Langerhans cell histiocytosis (LCH) is a disorder of myeloid neoplasia of dendritic cells that affects 1 in 200,000 children <15 years of age and even fewer adults. LCH presents with a spectrum of clinical manifestations. High-risk stratification is reserved for infiltration of blood, spleen, liver, and lungs. After decades of debate on the disease pathogenesis, a neoplastic mechanism is now favored on the basis of LCH cell clonality, rare cases of familial clustering, and recent evidence of mutations involving the Ras/Raf/MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathway in lesional biopsy specimens...
October 26, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29100280/impact-of-phosphoinositide-3-kinase-and-vitamin-d3-nuclear-receptor-single-nucleotide-polymorphisms-on-the-outcome-of-malignant-melanoma-patients
#7
Francesca Morgese, Davide Soldato, Silvia Pagliaretta, Riccardo Giampieri, Donatella Brancorsini, Mariangela Torniai, Silvia Rinaldi, Agnese Savini, Azzurra Onofri, Marina Scarpelli, Rossana Berardi
Background: Several studies associating single nucleotide polymorphisms (SNPs) frequencies with tumors outcome have been conducted, nevertheless malignant melanoma literature data are inconclusive.Therefore we evaluate the impact of different genotypes for phosphoinositide-3-kinase (PI3K) and vitamin D3 nuclear receptor (VDR) SNPs on melanoma patients' outcome. Materials and methods: Genomic DNA of 88 patients was extracted from blood and tumor samples. SNPs were determined by PCR using TaqMan assays...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29094484/degradation-of-ampk-%C3%AE-1-sensitizes-braf-inhibitor-resistant-melanoma-cells-to-arginine-deprivation
#8
Ying-Ying Li, Chunjing Wu, Sumedh S Shah, Shu-Mei Chen, Medhi Wangpaichitr, Macus T Kuo, Lynn G Feun, Xiaoqing Han, Miguel Suarez, Jeffrey Prince, Niramol Savaraj
Melanomas harboring BRAF mutation (V600E) are known to recur frequently following treatment with BRAF inhibitors (BRAFi) despite a high initial response rate. Our previous study has uncovered that BRAFi-resistant melanoma (BR) cells are vulnerable to arginine deprivation. It has been reported that naïve melanoma cells undergo autophagy and re-express argininosuccinate synthetase 1 (ASS1) to enable them to synthesize arginine for survival when encountering arginine deprivation. Abolishing these two factors in BR cells confers sensitivity to arginine deprivation...
November 2, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29070145/-effect-of-erk1-2-signaling-pathway-inhibitor-pd98059-on-the-expression-of-ras-braf-mek-erk1-2-in-marrow-nucleated-red-blood-cells-of-cms-patients
#9
Yuan-Fang Han, Lin-Hua Ji, Ting-Ting Feng, Fang Liu, Sen Cui, Juan Su
OBJECTIVE: To investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS). METHODS: Sixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29050218/braf-mek-inhibitors-promote-cd47-expression-that-is-reversible-by-erk-inhibition-in-melanoma
#10
Fen Liu, Chen Chen Jiang, Xu Guang Yan, Hsin-Yi Tseng, Chun Yan Wang, Yuan Yuan Zhang, Hamed Yari, Ting La, Margaret Farrelly, Su Tang Guo, Rick F Thorne, Lei Jin, Qi Wang, Xu Dong Zhang
The expression of CD47 on the cancer cell surface transmits "don't eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses. Here we report that oncogenic activation of ERK plays an important role in transcriptional activation of CD47 through nuclear respiratory factor 1 (NRF-1) in melanoma cells. Treatment with BRAF/MEK inhibitors upregulated CD47 in cultured melanoma cells and fresh melanoma isolates. Similarly, melanoma cells selected for resistance to the BRAF inhibitor vemurafenib expressed higher levels of CD47...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29045061/suppression-of-mapk-signaling-in-braf-activated-pten-deficient-melanoma-by-blocking-%C3%AE-catenin-signaling-in-cancer-associated-fibroblasts
#11
Linli Zhou, Kun Yang, Spencer Dunaway, Zalfa Abdel-Malek, Thomas Andl, Ana Luisa Kadekaro, Yuhang Zhang
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs...
October 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28982154/combined-mek-and-erk-inhibition-overcomes-therapy-mediated-pathway-reactivation-in-ras-mutant-tumors
#12
Mark Merchant, John Moffat, Gabriele Schaefer, Jocelyn Chan, Xi Wang, Christine Orr, Jason Cheng, Thomas Hunsaker, Lily Shao, Stephanie J Wang, Marie-Claire Wagle, Eva Lin, Peter M Haverty, Sheerin Shahidi-Latham, Hai Ngu, Margaret Solon, Jeffrey Eastham-Anderson, Hartmut Koeppen, Shih-Min A Huang, Jacob Schwarz, Marcia Belvin, Daniel Kirouac, Melissa R Junttila
Mitogen-activated protein kinase (MAPK) pathway dysregulation is implicated in >30% of all cancers, rationalizing the development of RAF, MEK and ERK inhibitors. While BRAF and MEK inhibitors improve BRAF mutant melanoma patient outcomes, these inhibitors had limited success in other MAPK dysregulated tumors, with insufficient pathway suppression and likely pathway reactivation. In this study we show that inhibition of either MEK or ERK alone only transiently inhibits the MAPK pathway due to feedback reactivation...
2017: PloS One
https://www.readbyqxmd.com/read/28953887/pak-signalling-drives-acquired-drug-resistance-to-mapk-inhibitors-in-braf-mutant-melanomas
#13
Hezhe Lu, Shujing Liu, Gao Zhang, Bin Wu, Yueyao Zhu, Dennie T Frederick, Yi Hu, Wenqun Zhong, Sergio Randell, Norah Sadek, Wei Zhang, Gang Chen, Chaoran Cheng, Jingwen Zeng, Lawrence W Wu, Jie Zhang, Xiaoming Liu, Wei Xu, Clemens Krepler, Katrin Sproesser, Min Xiao, Benchun Miao, Jianglan Liu, Claire D Song, Jephrey Y Liu, Giorgos C Karakousis, Lynn M Schuchter, Yiling Lu, Gordon Mills, Yusheng Cong, Jonathan Chernoff, Jun Guo, Genevieve M Boland, Ryan J Sullivan, Zhi Wei, Jeffrey Field, Ravi K Amaravadi, Keith T Flaherty, Meenhard Herlyn, Xiaowei Xu, Wei Guo
Targeted BRAF inhibition (BRAFi) and combined BRAF and MEK inhibition (BRAFi and MEKi) therapies have markedly improved the clinical outcomes of patients with metastatic melanoma. Unfortunately, the efficacy of these treatments is often countered by the acquisition of drug resistance. Here we investigated the molecular mechanisms that underlie acquired resistance to BRAFi and to the combined therapy. Consistent with previous studies, we show that resistance to BRAFi is mediated by ERK pathway reactivation. Resistance to the combined therapy, however, is mediated by mechanisms independent of reactivation of ERK in many resistant cell lines and clinical samples...
October 5, 2017: Nature
https://www.readbyqxmd.com/read/28951457/mechanisms-of-acquired-resistance-to-braf-v600e-inhibition-in-colon-cancers-converge-on-raf-dimerization-and-are-sensitive-to-its-inhibition
#14
Rona Yaeger, Zhan Yao, David M Hyman, Jaclyn F Hechtman, Efsevia Vakiani, HuiYong Zhao, Wenjing Su, Lu Wang, Andrew Joelson, Andrea Cercek, José Baselga, Elisa de Stanchina, Leonard Saltz, Michael F Berger, David B Solit, Neal Rosen
BRAF V600E colorectal cancers (CRC) are insensitive to RAF inhibitor monotherapy due to feedback reactivation of receptor tyrosine kinase signaling. Combined RAF and EGFR inhibition exerts a therapeutic effect, but resistance invariably develops through undefined mechanisms. In this study, we determined that CRC progression specimens invariably harbored lesions in elements of the RAS-RAF-MEK-ERK pathway. Genetic amplification of wild-type RAS was a recurrent mechanism of resistance in CRC patients that was not seen in similarly resistant melanomas...
September 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28947956/non-v600-braf-mutations-recurrently-found-in-lung-cancer-predict-sensitivity-to-the-combination-of-trametinib-and-dabrafenib
#15
Amir Noeparast, Erik Teugels, Philippe Giron, Gil Verschelden, Sylvia De Brakeleer, Lore Decoster, Jacques De Grève
Approximately half of BRAF-mutated Non-small cell lung cancers (NSCLCs) harbor a non-V600 BRAF mutation, accounting for ∼40,000 annual deaths worldwide. Recent studies have revealed the benefits of combined targeted therapy with a RAF-inhibitor (Dabrafenib) and a MEK-inhibitor (Trametinib) in treating V600 BRAF mutant cancers, including NSCLC. In contrast, sensitivity of non-V600 BRAF mutations to these inhibitors is not documented. Non-V600 mutations can either increase or impair BRAF kinase activity. However, impaired BRAF kinases can still activate the ERK pathway in a CRAF-dependent manner...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28939558/targeting-the-mapk-signaling-pathway-in-cancer-promising-preclinical-activity-with-the-novel-selective-erk1-2-inhibitor-bvd-523-ulixertinib
#16
Ursula A Germann, Brinley F Furey, William Markland, Russell R Hoover, Alex M Aronov, Jeffrey J Roix, Micheal Hale, Diane M Boucher, David A Sorrell, Gabriel Martinez-Botella, Matthew Fitzgibbon, Paul Shapiro, Michael J Wick, Ramin Samadani, Kathryn Meshaw, Anna Groover, Gary DeCrescenzo, Mark Namchuk, Caroline M Emery, Saurabh Saha, Dean J Welsch
Aberrant activation of signaling through the RAS-RAF-MEK-ERK (MAPK) pathway is implicated in numerous cancers, making it an attractive therapeutic target. Although BRAF- and MEK-targeted combination therapy has demonstrated significant benefit beyond single-agent options, the majority of patients develop resistance and disease progression after approximately 12 months. Reactivation of ERK signaling is a common driver of resistance in this setting. Here we report the discovery of BVD-523 (ulixertinib), a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and ERK1/2 selectivity...
September 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28938534/targeting-of-the-mapk-and-akt-pathways-in-conjunctival-melanoma-shows-potential-synergy
#17
Jinfeng Cao, Renier C Heijkants, Aart G Jochemsen, Mehmet Dogrusöz, Mark J de Lange, Pieter A van der Velden, Sjoerd H van der Burg, Martine J Jager, Robert M Verdijk
PURPOSE: Conjunctival melanoma (CM) is a rare but lethal form of cancer. Similar to cutaneous melanoma, CM frequently carries activating mutations in BRAF and NRAS. We studied whether CM as well as conjunctival benign and premalignant melanocytic lesions express targets in the mitogen-activated protein kinase (MAPK) and AKT pathways, and whether specific inhibitors can suppress CM growth in vitro. METHODS: 131 conjunctival lesions obtained from 129 patients were collected...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28921051/fine-particle-matters-induce-dna-damage-and-g2-m-cell-cycle-arrest-in-human-bronchial-epithelial-beas-2b-cells
#18
Jing Wu, Yanfeng Shi, Collins Otieno Asweto, Lin Feng, Xiaozhe Yang, Yannan Zhang, Hejing Hu, Junchao Duan, Zhiwei Sun
There is compelling evidence that exposure to particulate matter (PM) is linked to lung tumorigenesis. However, there is not enough experimental evidence to support the specific mechanisms of PM2.5-induced DNA damage and cell cycle arrest in lung tumorigenesis. In this study, we investigated the toxic effects and molecular mechanisms of PM2.5 on bronchial epithelial (BEAS-2B) cells. PM2.5 exposure reduced cell viability and enhanced LDH activity. The cell growth curves of BEAS-2B cells decreased gradually with the increase in PM2...
November 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28910386/dusp5-and-dusp6-two-erk-specific-phosphatases-are-markers-of-a-higher-mapk-signaling-activation-in-braf-mutated-thyroid-cancers
#19
Camille Buffet, Karine Hecale-Perlemoine, Léopoldine Bricaire, Florent Dumont, Camille Baudry, Frédérique Tissier, Jérôme Bertherat, Beatrix Cochand-Priollet, Marie-Laure Raffin-Sanson, Françoise Cormier, Lionel Groussin
BACKGROUND: Molecular alterations of the MAPK pathway are frequently observed in papillary thyroid carcinomas (PTCs). It leads to a constitutive activation of the signalling pathway through an increase in MEK and ERK phosphorylation. ERK is negatively feedback-regulated by Dual Specificity Phosphatases (DUSPs), especially two ERK-specific DUSPs, DUSP5 (nuclear) and DUSP6 (cytosolic). These negative MAPK regulators may play a role in thyroid carcinogenesis. METHODS: MAPK pathway activation was analyzed in 11 human thyroid cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28868020/erdheim-chester-disease-the-importance-of-information-integration
#20
Anna Nikonova, Khashayar Esfahani, Guillaume Chausse, Stephan Probst, Tina Petrogiannis-Haliotis, Hans Knecht, Genevieve Gyger
BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis disorder that utilizes the RAS-RAF-MEK-ERK pathway. It has a highly variable clinical presentation, where virtually any organ can be involved, thus having the potential of posing a great diagnostic challenge. Over half of the reported cases have the BRAF V600E mutation and have shown a remarkable response to vemurafenib. CASE PRESENTATION: We describe herein a patient with a history of stroke-like symptoms and retroperitoneal fibrosis that on initial pathology raised the possibility of IgG4-related disease...
May 2017: Case Reports in Oncology
keyword
keyword
77934
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"