keyword
MENU ▼
Read by QxMD icon Read
search

KRAS, RAS

keyword
https://www.readbyqxmd.com/read/28794806/recent-developments-in-the-treatment-of-metastatic-colorectal-cancer
#1
REVIEW
Jonathan M Loree, Scott Kopetz
Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28781083/kras-g12c-drug-development-discrimination-between-switch-ii-pocket-configurations-using-hydrogen-deuterium-exchange-mass-spectrometry
#2
Jia Lu, Rane A Harrison, Lianbo Li, Mei Zeng, Sudershan Gondi, David Scott, Nathanael S Gray, John R Engen, Kenneth D Westover
KRAS G12C, the most common RAS mutation found in non-small-cell lung cancer, has been the subject of multiple recent covalent small-molecule inhibitor campaigns including efforts directed at the guanine nucleotide pocket and separate work focused on an inducible pocket adjacent to the switch motifs. Multiple conformations of switch II have been observed, suggesting that switch II pocket (SIIP) binders may be capable of engaging a range of KRAS conformations. Here we report the use of hydrogen/deuterium-exchange mass spectrometry (HDX MS) to discriminate between conformations of switch II induced by two chemical classes of SIIP binders...
July 25, 2017: Structure
https://www.readbyqxmd.com/read/28776576/gnas-mutations-in-primary-mucinous-and-non-mucinous-lung-adenocarcinomas
#3
Lauren L Ritterhouse, Marina Vivero, Mari Mino-Kenudson, Lynette M Sholl, A John Iafrate, Valentina Nardi, Fei Dong
GNAS mutations have been described in mucinous and non-mucinous epithelial neoplasms of the appendix, pancreas, and colon, with hotspot GNAS mutations found in up to two-thirds of pancreatic intraductal papillary mucinous neoplasms. Additionally, many GNAS-mutated tumors have concurrent mutations in the Ras/Raf pathway. The clinicopathologic features of GNAS-mutated lung carcinomas, however, have not yet been characterized. Primary lung carcinomas from Brigham and Women's Hospital (n=1282) or Massachusetts General Hospital (n=1070) were genotyped on a targeted massively parallel sequencing panel of oncogenes and tumor suppressor genes including GNAS...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28767562/deleterious-effect-of-ras-and-evolutionary-high-risk-tp53-double-mutation-in-colorectal-liver-metastases
#4
Yun Shin Chun, Guillaume Passot, Suguru Yamashita, Maliha Nusrat, Panagiotis Katsonis, Jonathan M Loree, Claudius Conrad, Ching-Wei D Tzeng, Lianchun Xiao, Thomas A Aloia, Cathy Eng, Scott E Kopetz, Olivier Lichtarge, Jean-Nicolas Vauthey
OBJECTIVE: To assess the impact of somatic gene mutations on survival among patients undergoing resection of colorectal liver metastases (CLM). BACKGROUND: Patients undergoing CLM resection have heterogeneous outcomes, and accurate risk stratification is necessary to optimize patient selection for surgery. METHODS: Next-generation sequencing of 50 cancer-related genes was performed from primary tumors and/or liver metastases in 401 patients undergoing CLM resection...
August 1, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28765579/inhibition-of-akt1-signaling-promotes-invasion-and-metastasis-of-non-small-cell-lung-cancer-cells-with-k-ras-or-egfr-mutations
#5
Guanhua Rao, Mariaelena Pierobon, In-Kyu Kim, Wei-Hsun Hsu, Jianghong Deng, Yong-Wha Moon, Emanuel F Petricoin, Yu-Wen Zhang, Yisong Wang, Giuseppe Giaccone
Accumulating evidence supports a role of the PI3K-AKT pathway in the regulation of cell motility, invasion and metastasis. AKT activation is known to promote metastasis, however under certain circumstances, it also shows an inhibitory activity on metastatic processes, and the cause of such conflicting results is largely unclear. Here we found that AKT1 is an important regulator of metastasis and down-regulation of its activity is associated with increased metastatic potential of A549 cells. Inhibition of AKT1 enhanced migration and invasion in KRAS- or EGFR-mutant non-small cell lung cancer (NSCLC) cells...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760854/oncogenic-kras-and-p53-loss-drive-gastric-tumorigenesis-in-mice-that-can-be-attenuated-by-e-cadherin-expression
#6
Jacob Till, Changhwan Yoon, Bang-Jin Kim, Kerry C Roby, Prince Addai, Evan Jonokuchi, Laura H Tang, Sam S Yoon, Sandra Ryeom
Gastric adenocarcinoma (GA) is the third leading cause of cancer-related death worldwide, but no models exist to readily investigate distant metastases which are mainly responsible for mortality in this disease. Here we report the development of a genetically engineered mouse model of GA tumorigenesis based on Kras(G12D) expression plus inactivation of E-cadherin (Cdh1) and p53 in the gastric parietal cell lineage. Intestinal and diffuse gastric tumors arise rapidly in this model, which displays a median survival of 76 days...
July 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28759160/a-quadruple-action-pt-iv-prodrug-with-anticancer-activity-against-kras-mutated-cancer-cell-lines
#7
Dan Gibson, Emanuele Petruzzella, Jeremy Phillip Braude, Janice Aldrich-Wright, Valentina Gandin
We developed a novel Pt(IV) prodrug that simultaneously releases four different bioactive moieties inside the cancer cell acting like a cluster bomb. Its cytotoxicity against 2D and 3D cancer cells is significantly better than cisplatin. It is 200-450 fold more potent than cisplatin against KRAS mutated pancreatic and colon cancers and is 40 fold more selective towards KRAS mutated cells compared to non-cancerous. This is important since RAS proteins play a role in regulating cell differentiation, proliferation, and survival and KRAS is mutated in 90% of pancreatic adenocarcinomas, 45% of colorectal cancers, and 35% of lung adenocarcinomas...
July 31, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28736556/ras-signaling-inhibitors-attenuate-disease-in-adjuvant-induced-arthritis-via-targeting-pathogenic-antigen-specific-th17-type-cells
#8
Morad Zayoud, Victoria Marcu-Malina, Einav Vax, Jasmine Jacob-Hirsch, Galit Elad-Sfadia, Iris Barshack, Yoel Kloog, Itamar Goldstein
The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28732488/expression-of-the-scaffold-connector-enhancer-of-kinase-suppressor-of-ras-1-cnksr1-is-correlated-with-clinical-outcome-in-pancreatic-cancer
#9
Humair S Quadri, Taylor J Aiken, Michael Allgaeuer, Radim Moravec, Sean Altekruse, S Perwez Hussain, Markku M Miettinen, Stephen M Hewitt, Udo Rudloff
BACKGROUND: Despite the near universal occurrence of activating codon 12 KRAS somatic variants in pancreatic cancer, there is considerable heterogeneity in the molecular make-up, MAPK/ERK pathway activation states, and clinical outcome in this disease. We analyzed the expression levels of CNKSR1, a scaffold that influences MAPK/ERK pathway activity, in clinical pancreas cancer specimens and their impact on survival of patients with pancreatic cancer. METHODS: Immunohistochemical staining for CNKSR1 expression was performed on 120 specimens from three independent pancreatic cancer tissue registries, phospho-ERK levels were measured in 86 samples...
July 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28700943/a-role-for-mitochondrial-translation-in-promotion-of-viability-in-k-ras-mutant-cells
#10
Timothy D Martin, Danielle R Cook, Mei Yuk Choi, Mamie Z Li, Kevin M Haigis, Stephen J Elledge
Activating mutations in the KRAS oncogene are highly prevalent in tumors, especially those of the colon, lung, and pancreas. To better understand the genetic dependencies that K-Ras mutant cells rely upon for their growth, we employed whole-genome CRISPR loss-of-function screens in two isogenic pairs of cell lines. Since loss of essential genes is uniformly toxic in CRISPR-based screens, we also developed a small hairpin RNA (shRNA) library targeting essential genes. These approaches uncovered a large set of proteins whose loss results in the selective reduction of K-Ras mutant cell growth...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28695301/optimal-use-of-anti-egfr-monoclonal-antibodies-for-patients-with-advanced-colorectal-cancer-a-meta-analysis
#11
REVIEW
E J van Helden, C W Menke-van der Houven van Oordt, M W Heymans, J C F Ket, R van den Oord, H M W Verheul
This meta-analysis was performed to determine the optimal use of anti-EGFR mAb in the treatment of metastasized colorectal cancer (mCRC). Seventeen randomized clinical trials were included, all evaluating the added value of anti-EGFR mAb to standard treatment line in patients with KRAS wild-type mCRC. Hazard and odds ratios were pooled using a random effect model, weighted according to cohort size. Pooled data of six first- and two second-line studies demonstrated a significantly improved ORR (OR 1.62, CI 1...
July 10, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28693246/genetic-alterations-in-japanese-extrahepatic-biliary-tract-cancer
#12
Rei Noguchi, Kiyoshi Yamaguchi, Tsuneo Ikenoue, Yumi Terakado, Yasunori Ohta, Naohide Yamashita, Osamu Kainuma, Sana Yokoi, Yoshiaki Maru, Hiroki Nagase, Yoichi Furukawa
Biliary tract cancer (BTC) is one of the most devastating types of malignant neoplasms worldwide. However, the mechanisms underlying the development and progression of BTC remain unresolved. BTC includes extrahepatic bile duct carcinoma (EBDC), gallbladder carcinoma (GBC) and ampulla of Vater carcinoma (AVC), named according to the location of the tumor. Although genetic alterations of intrahepatic cholangiocarcinoma have been investigated, those of EBDC, GBC and AVC have not yet been fully understood. The present study analyzed somatic mutations of 50 cancer-associated genes in 27 Japanese BTC cells, including: 11 EBDC, 14 GBC and 2 AVC...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692881/detection-of-kras-exon-2-mutations-in-circulating-tumor-cells-isolated-by-the-iset-system-from-patients-with-ras-wild-type-metastatic-colorectal-cancer
#13
Alexios Matikas, Alexandra Voutsina, Eleni Lagoudaki, Dora Hatzidaki, Maria Trypaki, Giannis Stoupis, Maria Tzardi, Dimitrios Mavroudis, Vasilios Georgoulias
INTRODUCTION: The presence of KRAS mutations in patients with metastatic colorectal cancer (mCRC) predicts poor response to agents targeting the EGFR. Even in patients with RAS wild type (WT) tumors, resistance eventually develops due to multiple mechanisms, including the expansion of previously undetected KRAS mutated clones. In this feasibility study, we aimed to detect KRAS exon 2 mutations in serial samples of circulating tumor cells (CTCs) of RAS WT patients with mCRC captured by the Isolation by Size of Epithelial Tumor cells (ISET) system...
August 2017: Translational Oncology
https://www.readbyqxmd.com/read/28692044/pyruvate-dehydrogenase-kinase-4-exhibits-a-novel-role-in-the-activation-of-mutant-kras-regulating-cell-growth-in-lung-and-colorectal-tumour-cells
#14
A G Trinidad, N Whalley, R Rowlinson, O Delpuech, P Dudley, C Rooney, S E Critchlow
RAS signalling is involved in the control of several metabolic pathways including glycolysis, mitochondrial respiration and glutamine metabolism. Importantly, we have found here that loss of PDHK4, a key regulator of the pyruvate dehydrogenase complex, caused a profound cell growth inhibition in tumour cells harbouring KRAS mutations. Using isogenic cells and a panel of colorectal and lung cell lines we demonstrated that KRAS mutant cells showed a dependency on PDHK4 whereas KRAS wild-type cells were significantly resistant to PDHK4 knockdown...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28688743/-detection-of-ras-genes-mutation-using-the-cobas-%C3%A2-method-in-a-private-laboratory-of-pathology-medical-and-economical-study-in-comparison-to-a-public-platform-of-molecular-biology-of-cancer
#15
Anne-Flore Albertini, Delphine Raoux, Frédéric Neumann, Stéphane Rossat, Farid Tabet, Florence Pedeutour, Valérie Duranton-Tanneur, Valérie Kubiniek, Olivier Vire, Nicolas Weinbreck
In France, determination of the mutation status of RAS genes for predictive response to anti-EGFR targeted treatments is carried out by public platforms of molecular biology of cancer created by the French National Cancer Institute. This study aims to demonstrate the feasibility of these analyses by a private pathology laboratory (MEDIPATH) as per the requirements of accreditation. We retrospectively studied the mutation status of KRAS and NRAS genes in 163 cases of colorectal metastatic cancer using the Cobas(®) technique...
July 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28685087/heterogeneity-in-the-colorectal-primary-tumor-and-the-synchronous-resected-liver-metastases-prior-to-and-after-treatment-with-an-anti-egfr-monoclonal-antibody
#16
Daniela Adua, Francesca Di Fabio, Giorgio Ercolani, Michelangelo Fiorentino, Elisa Gruppioni, Annalisa Altimari, Fabiola Lorena Rojas Limpe, Nicola Normanno, Antonio Daniele Pinna, Carmine Pinto
Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28682649/targeting-ras-signaling-in-aml-ralb-is-a-small-gtpase-with-big-potential
#17
Emily J Pomeroy, Craig E Eckfeldt
Acute myeloid leukemia (AML) is a devastating malignancy for which novel treatment approaches are desperately needed. Ras signaling is an attractive therapeutic target for AML because a large proportion of AMLs have mutations in NRAS, KRAS, or genes that activate Ras signaling, and key Ras effectors are activated in virtually all AML patient samples. This has inspired efforts to develop Ras-targeted treatment strategies for AML. Due to the inherent difficulty and disappointing efficacy of targeting Ras proteins directly, many have focused on inhibiting Ras effector pathways...
July 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28675058/selumetinib-for-the-treatment-of-non-small-cell-lung-cancer
#18
REVIEW
Francesca Casaluce, Assunta Sgambato, Paolo Maione, Paola Claudia Sacco, Giuseppe Santabarbara, Cesare Gridelli
KRAS is the most frequently mutated oncogene in NSCLC, occurring in around a third of patients. However, this largest genomically defined subgroup of lung cancer patients seem to remain 'undruggable', with any effective targeted therapy approved at the moment. The prognostic and predictive power and thus the clinical utility of KRAS oncogenic mutations in lung cancer are highly debated issues, not supportive of KRAS testing in clinical practice of NSCLC therapy. Areas covered: A phase II trial in KRAS-mutant NSCLC had shown significant improvements in PFS and ORR in patients treated with selumetinib plus docetaxel compared to docetaxel alone...
August 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28674184/steady-state-levels-of-phosphorylated-mitogen-activated-protein-kinase-kinase-1-2-determined-by-mortalin-hspa9-and-protein-phosphatase-1-alpha-in-kras-and-braf-tumor-cells
#19
Pui-Kei Wu, Seung-Keun Hong, Jong-In Park
Although deregulation of MEK/ERK activity is a key feature in cancer, high magnitude MEK/ERK activity can paradoxically induce growth inhibition. Therefore, additional mechanisms may exist to modulate MEK/ERK activity in favor of tumor cell proliferation. We previously reported that mortalin/HSPA9 can facilitate proliferation of certain KRAS- and BRAF-tumor cells by modulating MEK/ERK activity. In this study, we demonstrate that mortalin can regulate MEK/ERK activity via protein phosphatase 1α (PP1α). We found that PP1α inhibition increases steady-state levels of phosphorylated MEK1/2 in various tumor cells expressing B-Raf(V600E) or K-Ras(G12D/V) Intriguingly, co-immunoprecipitation and in vitro binding assays revealed that mortalin facilitates PP1α-mediated MEK1/2 dephosphorylation by promoting PP1α-MEK1/2 interaction in an ATP-sensitive manner...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28671043/oncogene-mutation-profile-predicts-tumor-regression-and-survival-in-locally-advanced-rectal-cancer-patients-treated-with-preoperative-chemoradiotherapy-and-radical-surgery
#20
Jianhong Peng, Junzhong Lin, Miaozhen Qiu, Yujie Zhao, Yuxiang Deng, Jianyong Shao, Peirong Ding, Huizhong Zhang, Desen Wan, Zhenhai Lu, Zhizhong Pan
Tumor response to preoperative chemoradiotherapy and postoperative survival differs among patients with locally advanced rectal cancer. The objective was to find correlations of mutated oncogenes and clinical outcomes in locally advanced rectal cancer. A total of 70 patients with preoperative preoperative chemoradiotherapy followed by radical surgery at a single cancer center between 2006 and 2012 were enrolled. Pretreatment tumor biopsy samples were assayed for 238 mutation hotspots harboring 19 oncogenes by time-of-flight mass spectrometry and OncoCarta Array...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
keyword
keyword
18607
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"