keyword
MENU ▼
Read by QxMD icon Read
search

KRAS, RAS

keyword
https://www.readbyqxmd.com/read/28314765/no-back-seat-for-a-progression-event-k-ras-as-a-therapeutic-target-in-crc
#1
REVIEW
Emily J Poulin, Kevin M Haigis
KRAS is the most frequently mutated oncogene in human cancer and plays a central, although poorly understood, role in colorectal cancer (CRC) progression. In this issue of Genes & Development, Boutin and colleagues (pp. 370-382) present a new mouse model of CRC in which the expression of oncogenic K-RAS is regulated by doxycycline. Using this model, they demonstrate that continued expression of oncogenic K-RAS is required for the survival of primary and metastatic colon cancers and that oncogenic K-RAS activates TGF-β signaling to promote tumor invasion and metastasis...
February 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28314739/intratumorous-heterogeneity-for-ras-mutations-in-a-treatment-na%C3%A3-ve-colorectal-tumour
#2
Sebastian Lunke, Belinda Lee, Sevastjan Kranz, Peter Gibbs, Paul Waring, Michael Christie
Activating mutations in KRAS and NRAS genes in patients with colorectal cancer (CRC) are associated with a lack of response to treatment with anti-epidermal growth factor receptor (EGFR) therapies. Mutations in these genes are thought to be mutually exclusive, however reports have described CRCs with two activating rat sarcoma (RAS) mutations. This has fuelled discussion about whether these mutations are the result of intratumorous heterogeneity, or if they are co-occurring in the same cancer cell clone. We present a case of a colorectal tumour with three RAS mutations detected during routine diagnostic testing...
March 17, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28306189/map4k4-is-a-novel-mapk-erk-pathway-regulator-required-for-lung-adenocarcinoma-maintenance
#3
Xuan Gao, Guangming Chen, Chenxi Gao, Dennis Han Zhang, Shih-Fan Kuan, Laura P Stabile, Guoxiang Liu, Jing Hu
About 76% of lung adenocarcinoma patients harbor activating mutations in the receptor tyrosine kinase (RTK)/RAS/RAF pathways, leading to aberrant activation of the MAPK pathways particularly the MAPK/ERK pathway. However, many lung adenocarcinomas lacking these genomic mutations also display significant MAPK pathway activation, suggesting that additional MAPK pathway alterations remain undetected. This study has identified serine/threonine kinase mitogen-activated protein 4 kinase 4 (MAP4K4) as a novel positive regulator of MAPK/ERK signaling in lung adenocarcinoma...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28292938/combinatorial-screening-of-pancreatic-adenocarcinoma-reveals-sensitivity-to-drug-combinations-including-bromodomain-inhibitor-plus-neddylation-inhibitor
#4
Casey G Langdon, James T Platt, Robert E Means, Pinar Iyidogan, Ramanaiah Mamillapalli, Michael Klein, Matthew A Held, Jong Woo Lee, Ja Seok Koo, Christos Hatzis, Howard S Hochster, David F Stern
Pancreatic adenocarcinoma (PDAC) is the fourth most common cause of cancer death in the United States. PDAC is difficult to manage effectively, with a five-year survival rate of only 5%. PDAC is largely driven by activating KRAS mutations, and as such, cannot be directly targeted with therapeutic agents that affect the activated protein. Instead, inhibition of downstream signaling and other targets will be necessary to effectively manage PDAC. Here, we describe a tiered single-agent and combination compound screen to identify targeted agents that impair growth of a panel of PDAC cell lines...
March 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28262927/targeting-the-ras-signaling-pathway-as-a-potential-therapeutic-target-in-the-treatment-of-colorectal-cancer
#5
REVIEW
Afsane Bahrami, Seyed Mahdi Hassanian, Soodabeh ShahidSales, Zahra Farjami, Malihe Hasanzadeh, Kazem Anvari, Amir Aledavood, Mina Maftouh, Gordon A Ferns, Majid Khazaei, Amir Avan
The V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is an important pathways that is frequently dysregulated in colorectal cancer (CRC). It is involved in the modulation of several downstream effectors, that include: Raf/Mek/Erk, PI3K/Akt, RalGDS/p38MAPK and Rac/Rho, and thereby influences tumorigenesis, the invasive behaviors of tumor cell, and resistance to therapy. There is growing evidence exploring the use of drugs that target these pathways in the treatment of CRC. Cetuximab has been approved for CRC patients without a KRAS mutation, or for EGFR-expressing metastatic CRC, although most of the patients have a mutation of KRAS and NRAS...
March 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28260928/long-term-survival-after-a-favorable-response-to-anti-egfr-antibody-plus-chemotherapy-to-treat-bone-marrow-metastasis-a-case-report-of-kras-wildtype-rectal-cancer
#6
Sho Nakamura, Tadahisa Fukui, Shuhei Suzuki, Hiroyuki Takeda, Kaname Watanabe, Takashi Yoshioka
Bone marrow metastasis is a rare consequence of colorectal cancer that results in a poor prognosis; few reports describe a favorable response to doublet chemotherapy combined with targeted therapy, which is currently the standard treatment. We experienced a case where anti-epidermal growth factor receptor (EGFR) antibody produced a marked anti-tumor response to bone marrow metastasis that led to long-term survival. A 51-year-old man was diagnosed with a primary KRAS-wildtype rectal cancer with multiple metastases, including the bone marrow...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28259104/association-of-oncogenic-mutations-in-patients-with-advanced-cutaneous-squamous-cell-carcinomas-treated-with-cetuximab
#7
Alexandra Picard, Florence Pedeutour, Frédéric Peyrade, Laurence Saudes, Valérie Duranton-Tanneur, Emmanuel Chamorey, Nathalie Cardot-Leccia, Anne Sudaka, Marc Ettaiche, Maxime Benchetrit, Gilles Poissonnet, Nicolas Weinbreck, Bérengère Dadone, Jean-Philippe Lacour, Thierry Passeron, Henri Montaudié
Importance: Cetuximab was recently proposed for advanced cutaneous squamous cell carcinomas (cSCC); however, its efficacy is inconsistent and identification of predictive biomarkers for response is necessary. Objective: To search for somatic mutations of the HRAS, KRAS, NRAS, BRAF, and EGFR genes in patients with advanced cSCC treated with cetuximab; and to investigate the efficacy and tolerance of cetuximab according to these mutations. Design, Setting, and Participants: A multicentric and retrospective study of 31 patients (22 men, 9 women) with histologically confirmed advanced cSCC carried out in 1 department of dermatology and 2 departments of medical oncology in France between January 2008 and December 2014...
March 4, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28237867/exploratory-analysis-of-biomarkers-associated-with-clinical-outcomes-from-the-study-of-lenvatinib-in-differentiated-cancer-of-the-thyroid
#8
Makoto Tahara, Martin Schlumberger, Rossella Elisei, Mouhammed Amir Habra, Naomi Kiyota, Ralf Paschke, Corina E Dutcus, Taro Hihara, Shannon McGrath, Mark Matijevic, Tadashi Kadowaki, Yasuhiro Funahashi, Steven I Sherman
BACKGROUND: Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in the phase III Study of (E7080) LEnvatinib in differentiated Cancer of the Thyroid (SELECT) of patients with radioiodine-refractory differentiated thyroid cancer. This exploratory analysis investigated potential predictive biomarkers of lenvatinib efficacy and target engagement. PATIENTS AND METHODS: Circulating cytokine/angiogenic factors (CAFs) in blood samples collected at baseline and throughout treatment were analysed from patients randomised to receive lenvatinib or placebo from August 5, 2011 to October 4, 2012...
February 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28237539/rationale-for-and-design-of-the-paradigm-study-randomized-phase-iii-study-of-mfolfox6-plus-bevacizumab-or-panitumumab-in-chemotherapy-na%C3%A3-ve-patients-with-ras-kras-nras-wild-type-metastatic-colorectal%C3%A2-cancer
#9
Takayuki Yoshino, Hiroyuki Uetake, Katsuya Tsuchihara, Kohei Shitara, Kentaro Yamazaki, Eiji Oki, Takeo Sato, Takeshi Naitoh, Yoshito Komatsu, Takeshi Kato, Kazunori Yamanaka, Kouji Iwasaki, Jumpei Soeda, Masamitsu Hihara, Takeharu Yamanaka, Atsushi Ochiai, Kei Muro
BACKGROUND: It remains unclear whether an anti-VEGF or anti-EGFR antibody with standard doublet chemotherapy is the optimal first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC). Here we outline the PARADIGM study (NCT02394795), designed to evaluate the superiority of panitumumab over bevacizumab, in combination with oxaliplatin/5-fluorouracil/leucovorin (mFOLFOX6) in patients with RAS wild-type chemotherapy-naïve mCRC. PATIENTS AND METHODS: Eligible patients are aged 20 to 79 years with an ECOG performance status of 0-1 and histologically/cytologically confirmed RAS wild-type mCRC...
January 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28223103/her2-amplification-and-cetuximab-efficacy-in-patients-with-metastatic-colorectal-cancer-harboring-wild-type-ras-and-braf
#10
Jae Ho Jeong, Jihun Kim, Yong Sang Hong, Dalyong Kim, Jeong Eun Kim, Sun Young Kim, Kyu-Pyo Kim, Young-Kwang Yoon, Deokhoon Kim, Sung-Min Chun, Yangsoon Park, Se Jin Jang, Tae Won Kim
BACKGROUND: Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harboring wild-type RAS. Human epidermal growth factor receptor 2 (HER2) amplification may be a mechanism of cetuximab resistance. We evaluated the association between HER2 amplification and cetuximab efficacy in patients with mCRC harboring wild-type RAS and BRAF. PATIENTS AND METHODS: Between December 2003 and June 2013, we identified 142 patients with mCRC whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF using high throughput sequencing (OncoMap version 4...
January 25, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28219002/molecular-testing-for-gastrointestinal-cancer
#11
REVIEW
Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2-4). A BRAF mutation is required for predicting poor prognosis...
March 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28202525/oncogenic-effects-of-high-mapk-activity-in-colorectal-cancer-mark-progenitor-cells-and-persist-irrespective-of-ras-mutations
#12
Cristina Blaj, Eva Marina Schmidt, Sebastian Lamprecht, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
About 40% of colorectal cancers have mutations in KRAS accompanied by downstream activation of MAPK signaling which promotes tumor invasion and progression. Here we report that MAPK signaling shows strong intratumoral heterogeneity and unexpectedly remains regulated in colorectal cancer irrespective of KRAS mutation status. Using primary colorectal cancer tissues, xenograft models and MAPK reporter constructs, we showed that tumor cells with high MAPK activity resided specifically at the leading tumor edge, ceased to proliferate, underwent epithelial-mesenchymal transition (EMT), and expressed markers related to colon cancer stem cells...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28193718/h-ras-isoform-mediates-protection-against-pressure-overload-induced-cardiac-dysfunction-in-part-through-activation-of-akt
#13
Takahisa Matsuda, Jae Im Jeong, Shohei Ikeda, Takanobu Yamamoto, Shumin Gao, Gopal J Babu, Peiyong Zhai, Dominic P Del Re
BACKGROUND: In general, Ras proteins are thought to promote cardiac hypertrophy, an important risk factor for cardiovascular disease and heart failure. However, the contribution of different Ras isoforms has not been investigated. The objective of this study was to define the role of H- and K-Ras in modulating stress-induced myocardial hypertrophy and failure. METHODS AND RESULTS: We used H- and K-Ras gene knockout mice and subjected them to pressure overload to induce cardiac hypertrophy and dysfunction...
February 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28192404/isoprenylcysteine-carboxylmethyltransferase-is-critical-for-malignant-transformation-and-tumor-maintenance-by-all-ras-isoforms
#14
H Y Lau, J Tang, P J Casey, M Wang
Despite extensive effort, there has been limited progress in the development of direct RAS inhibitors. Targeting isoprenylcysteine carboxylmethyltransferase (ICMT), a unique enzyme of RAS post-translational modification, represents a promising strategy to inhibit RAS function. However, there lacks direct genetic evidence on the role of ICMT in RAS-driven human cancer initiation and maintenance. Using CRISPR/Cas9 genome editing, we have created Icmt loss-of-function isogenic cell lines for both RAS-transformed human mammary epithelial cells (HME1) and human cancer cell lines MiaPaca-2 and MDA-MB-231 containing naturally occurring mutant KRAS...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28188750/kras-and-pik3ca-mutations-in-colorectal-adenocarcinomas-correlate-with-aggressive-histological-features-and-behavior
#15
Sejin Jang, Mineui Hong, Mi Kyung Shin, Byung Chun Kim, Hyung-Sik Shin, Eunsil Yu, Seung-Mo Hong, Jihun Kim, Sung Min Chun, Tae-Im Kim, Kyung-Chan Choi, Young Woong Ko, Jeong Won Kim
Tumor budding (TB) in colorectal carcinoma (CRC) is related to epithelial-mesenchymal transition (EMT) and has been recently characterized as an indicator of poor prognosis along with lymphovascular tumor emboli (LVE), perineural invasion (PNI), and an infiltrative growth pattern. Mutations in the genes of the Ras-MAPK and PI3K pathways are associated with EMT and an aggressive CRC phenotype and have been used in patient stratification for anti-EGF receptor therapies; however, the impact of these mutations on CRC morphology and behavior remains unclear...
February 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28188683/functional-kras-mutations-and-a-potential-role-for-pi3k-akt-activation-in-wilms-tumors
#16
Dina Polosukhina, Harold D Love, Hernan Correa, Zengliu Su, Kimberly B Dahlman, William Pao, Harold L Moses, Carlos L Arteaga, Harold N Lovvorn, Roy Zent, Peter E Clark
Wilms tumor (WT) is the most common renal neoplasm of childhood and affects 1 in 10,000 children aged less than 15 years. These embryonal tumors are thought to arise from primitive nephrogenic rests that derive from the metanephric mesenchyme during kidney development and are characterized partly by increased Wnt/β-catenin signaling. We previously showed that coordinate activation of Ras and β-catenin accelerates the growth and metastatic progression of a murine WT model. Here, we show that activating KRAS mutations can be found in human WT...
February 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28184012/chromosome-20q-amplification-defines-a-subtype-of-microsatellite-stable-left-sided-colon-cancers-with-wild-type-ras-raf-and-better-overall-survival
#17
Ryan N Ptashkin, Carlos Pagan, Rona Yaeger, Sumit Middha, Jinru Shia, Kevin P O'Rourke, Michael F Berger, Lu Wang, Robert Cimera, Jiajing Wang, David S Klimstra, Leonard Saltz, Marc Ladanyi, Ahmet Zehir, Jaclyn F Hechtman
Here comprehensive analysis was performed on the molecular and clinical features of colorectal carcinoma (CRC) harboring chromosome 20q amplification. Tumor and normal DNA from patients with advanced CRC underwent next generation sequencing (NGS) via MSK-IMPACT and a subset of case samples were subjected to high resolution microarray (Oncoscan). Relationships between genomic copy number and transcript expression were assessed with The Cancer Genome Atlas (TCGA) CRC data. Of the CRC patients sequenced (n=401) with MSK-IMPACT, 148 (37%) had 20q gain, and 30 (7%) had 20q amplification...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28179601/regulation-of-ras-signaling-and-function-by-plasma-membrane-microdomains
#18
Lawrence E Goldfinger, James V Michael
Together H-, N- and KRAS mutations are major contributors to ~30% of all human cancers. Thus, Ras inhibition remains an important anti-cancer strategy. The molecular mechanisms of isotypic Ras oncogenesis are still not completely understood. Monopharmacological therapeutics have not been successful in the clinic. These disappointing outcomes have led to attempts to target elements downstream of Ras, mainly targeting either the Phosphatidylinositol 3-Kinase (PI3K) or Mitogen-Activated Protein Kinase (MAPK) pathways...
February 7, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#19
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178529/atxn1l-cic-and-ets-transcription-factors-modulate-sensitivity-to-mapk-pathway-inhibition
#20
Belinda Wang, Elsa Beyer Krall, Andrew James Aguirre, Miju Kim, Hans Ragnar Widlund, Mihir Bhavik Doshi, Ewa Sicinska, Rita Sulahian, Amy Goodale, Glenn Spencer Cowley, Federica Piccioni, John Gerard Doench, David Edward Root, William Chun Hahn
Intrinsic resistance and RTK-RAS-MAPK pathway reactivation has limited the effectiveness of MEK and RAF inhibitors (MAPKi) in RAS- and RAF-mutant cancers. To identify genes that modulate sensitivity to MAPKi, we performed genome-scale CRISPR-Cas9 loss-of-function screens in two KRAS mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib. Loss of CIC, a transcriptional repressor of ETV1, ETV4, and ETV5, promoted survival in the setting of MAPKi in cancer cells derived from several lineages...
February 7, 2017: Cell Reports
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"