Ras

Summary

Gene Symbol: Ras
Description: KRAS proto-oncogene, GTPase
Alias: C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A, K-RAS4B, KI-RAS, KRAS1, KRAS2, NS3, RALD, RASK2, c-Ki-ras2, GTPase KRas, K-Ras 2, K-ras p21 protein, Kirsten rat sarcoma viral oncogene homolog, PR310 c-K-ras oncogene, c-Ki-ras, c-Kirsten-ras protein, cellular c-Ki-ras2 proto-oncogene, cellular transforming proto-oncogene, oncogene KRAS2, transforming protein p21, v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog
Species: human

Top Publications

  1. ncbi BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status
    Shi Yang
    Department of Pathology, Boston Medical Center, Boston, MA 02118, USA
    Am J Surg Pathol 28:1452-9. 2004
  2. doi KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial
    Susan D Richman
    Leeds Institute of Molecular Medicine, St James s Institute of Oncology, Cancer Research UK Genomic Services, University of Leeds, Leeds, UK
    J Clin Oncol 27:5931-7. 2009
  3. doi Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer
    Jean Yves Douillard
    Institut de Cancérologie de l Ouest ICO René Gauducheau, Nantes, France
    N Engl J Med 369:1023-34. 2013
  4. doi Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis
    Wendy De Roock
    Centre for Human Genetics, KU Leuven, Leuven, Belgium
    Lancet Oncol 11:753-62. 2010
  5. doi Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer
    Jolien Tol
    Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    N Engl J Med 360:563-72. 2009
  6. doi Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer
    Pierre Laurent-Puig
    INSERM UMR S775 Molecular Basis of Xenobiotics Response, Paris, France
    J Clin Oncol 27:5924-30. 2009
  7. doi Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer
    Helena Linardou
    1st Department of Medical Oncology, Metropolitan Hospital, Athens, Greece
    Lancet Oncol 9:962-72. 2008
  8. doi PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer
    Fotios Loupakis
    Department of Oncology, Azienda USL 6, Istituto Toscano Tumori, Livorno, Italy
    J Clin Oncol 27:2622-9. 2009
  9. ncbi Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes
    C Almoguera
    Department of Biochemistry, State University of New York, Stony Brook 11794
    Cell 53:549-54. 1988
  10. pmc Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
    David A Barbie
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115 USA
    Nature 462:108-12. 2009

Research Grants

  1. MARK REID PHILIPS; Fiscal Year: 2015
  2. FREDERICK DEECHEN TSAI; Fiscal Year: 2014
  3. Christopher M Counter; Fiscal Year: 2016
  4. Immune Mechanisms of HCV Persistence and Pathogenesis
    Jiaren Sun; Fiscal Year: 2012
  5. Brett D Lindenbach; Fiscal Year: 2016
  6. Dendritic cell targeted hepatitis c virus immunotherapy
    Tyler Curiel; Fiscal Year: 2003
  7. Novel Strategy for HCV NS3 Inhibitor Discovery
    Steven Ogata; Fiscal Year: 2001
  8. A Small Molecule to Activate Cetuximab to Kill K-RAS Mutant Colorectal Tumors
    Barry Jones; Fiscal Year: 2013
  9. Nancy R Zhang; Fiscal Year: 2015
  10. Warren N Schmidt; Fiscal Year: 2016

Detail Information

Publications393 found, 100 shown here

  1. ncbi BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status
    Shi Yang
    Department of Pathology, Boston Medical Center, Boston, MA 02118, USA
    Am J Surg Pathol 28:1452-9. 2004
    ..In contrast, the association of higher levels of CpG island methylation with more advanced histologic changes suggests that CpG island methylation plays a role in serrated polyp progression toward colorectal carcinoma...
  2. doi KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial
    Susan D Richman
    Leeds Institute of Molecular Medicine, St James s Institute of Oncology, Cancer Research UK Genomic Services, University of Leeds, Leeds, UK
    J Clin Oncol 27:5931-7. 2009
    ..We wanted to determine whether KRAS and/or BRAF mutation is also a predictive biomarker for other aCRC therapies...
  3. doi Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer
    Jean Yves Douillard
    Institut de Cancérologie de l Ouest ICO René Gauducheau, Nantes, France
    N Engl J Med 369:1023-34. 2013
    ..Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy.
  4. doi Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis
    Wendy De Roock
    Centre for Human Genetics, KU Leuven, Leuven, Belgium
    Lancet Oncol 11:753-62. 2010
    ....
  5. doi Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer
    Jolien Tol
    Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    N Engl J Med 360:563-72. 2009
    ..We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer...
  6. doi Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer
    Pierre Laurent-Puig
    INSERM UMR S775 Molecular Basis of Xenobiotics Response, Paris, France
    J Clin Oncol 27:5924-30. 2009
    ..However, only half of these patients will benefit from treatment, suggesting the need to identify additional biomarkers for cetuximab-based treatment efficacy...
  7. doi Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer
    Helena Linardou
    1st Department of Medical Oncology, Metropolitan Hospital, Athens, Greece
    Lancet Oncol 9:962-72. 2008
    Somatic mutations of the k-RAS oncogene have been assessed as a mechanism of de-novo resistance to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibition in patients with non-small-cell lung cancer (NSCLC), and to anti-EGFR ..
  8. doi PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer
    Fotios Loupakis
    Department of Oncology, Azienda USL 6, Istituto Toscano Tumori, Livorno, Italy
    J Clin Oncol 27:2622-9. 2009
    ..This retrospective study investigated the role of PTEN loss, AKT phosphorylation, and KRAS mutations on the activity of cetuximab plus irinotecan in patients with metastatic colorectal cancer (mCRC)...
  9. ncbi Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes
    C Almoguera
    Department of Biochemistry, State University of New York, Stony Brook 11794
    Cell 53:549-54. 1988
    ..chain reaction (PCR) and mutation detection by the RNAase A mismatch cleavage method, we have examined c-K-ras genes in human pancreatic carcinomas...
  10. pmc Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
    David A Barbie
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115 USA
    Nature 462:108-12. 2009
    ..These observations indicate that TBK1 and NF-kappaB signalling are essential in KRAS mutant tumours, and establish a general approach for the rational identification of co-dependent pathways in cancer...
  11. doi Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer
    Rafael G Amado
    Amgen, Inc, One Amgen Center Dr, MS 38 2 B, Thousand Oaks, CA 91320 1799, USA
    J Clin Oncol 26:1626-34. 2008
    ..Although activating mutations in KRAS, a small G-protein downstream of EGFR, correlate with poor response to anti-EGFR antibodies in mCRC, their role as a selection marker has not been established in randomized trials...
  12. doi KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer
    Jeanne Tie
    Ludwig Colon Cancer Initiative Laboratory, Ludwig Institute for Cancer Research, Parkville, Melbourne, Australia
    Clin Cancer Res 17:1122-30. 2011
    ..Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse...
  13. doi The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer
    Madhu S Kumar
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Cell 149:642-55. 2012
    ..the most frequent cause of cancer deaths worldwide; nearly half contain mutations in the receptor tyrosine kinase/RAS pathway. Here we show that RAS-pathway mutant NSCLC cells depend on the transcription factor GATA2...
  14. doi KRAS mutations in non-small cell lung cancer
    Gregory J Riely
    Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Am Thorac Soc 6:201-5. 2009
    ..In this review, we summarize the initial discovery of RAS mutations in NSCLC, describe work exploring associations with clinical factors and outcomes, and provide an ..
  15. doi Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab
    Jolien Tol
    Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Eur J Cancer 46:1997-2009. 2010
    ..Here we assess the predictive value of other potential relevant markers involved in the epidermal growth factor receptor (EGFR) signalling pathways for response to cetuximab-based treatment...
  16. doi Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer
    Cecily P Vaughn
    ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA
    Genes Chromosomes Cancer 50:307-12. 2011
    ..In total, 140/513 (27.3%) tumors wildtype for KRAS codons 12 and 13 harbored a mutation in another of the RAS pathway genes...
  17. doi Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab
    Sabine Tejpar
    Digestive Oncology Unit, University Hospital Gasthuisberg, Herestraat 49, Leuven, Belgium B 3000
    J Clin Oncol 30:3570-7. 2012
    ..We investigated in the first-line setting our previous finding that patients with chemorefractory KRAS G13D-mutated metastatic colorectal cancer (mCRC) benefit from cetuximab treatment...
  18. pmc A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk
    Elena Ratner
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Cancer Res 70:6509-15. 2010
    ....
  19. doi Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer
    Gordon Hutchins
    Leeds Institute of Molecular Medicine, Leeds University, United Kingdom
    J Clin Oncol 29:1261-70. 2011
    ..We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy...
  20. pmc Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells
    Jihye Yun
    Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Science 325:1555-9. 2009
    ..Together, these data suggest that glucose deprivation can drive the acquisition of KRAS pathway mutations in human tumors...
  21. doi Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial
    Arnaud D Roth
    Oncosurgery, Geneva UniversityHospital, Geneva, Switzerland
    J Clin Oncol 28:466-74. 2010
    ..We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting...
  22. doi The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients
    A Fariña-Sarasqueta
    Department of Molecular Diagnostics, Catharina Hospital Eindhoven, The Netherlands
    Ann Oncol 21:2396-402. 2010
    ..We determined the effects on clinical outcome of the BRAF mutation, microsatellite instability (MSI) and KRAS mutations in stage II and stage III colon carcinoma...
  23. pmc A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers
    Brock C Christensen
    Department of Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, USA
    Carcinogenesis 30:1003-7. 2009
    ..7; 95% CI, 1.4-5.3). These data demonstrate that cases with the KRAS-LCS6 variant have significantly reduced survival time and suggest that this variant may alter the phenotype or therapeutic response of this disease...
  24. doi Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer
    Jens Neumann
    Department of Pathology, Ludwig Maximilians Universitat Munchen, Thalkirchner Strasse 36, 80337 Munich, Germany
    Pathol Res Pract 205:858-62. 2009
    ..Thus, a mutation frequency of 40% and a cluster of three mutation types (p.G12D, pG12V, and p.G13D) in primaries and metastases can be defined as benchmarks for routine KRAS analyses...
  25. doi Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab
    Bart Jacobs
    Department of Pathology, Digestive Oncology Unit, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium
    J Clin Oncol 27:5068-74. 2009
    ....
  26. pmc PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer
    Shuji Ogino
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 44 Binney St, Room JF 215C, Boston, MA 02115 USA
    J Clin Oncol 27:1477-84. 2009
    ..PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little is known about the prognostic role of PIK3CA mutation in colon cancer...
  27. pmc Clinical significance of K-ras and BRAF mutations in Chinese colorectal cancer patients
    Hong Shen
    Department of Oncology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, Zhejiang Province, China
    World J Gastroenterol 17:809-16. 2011
    To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.
  28. pmc Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial
    Matthew T Seymour
    Cancer Medicine and Pathology, University of Leeds, Leeds, UK
    Lancet Oncol 14:749-59. 2013
    ..Our aim was to assess the addition of panitumumab to irinotecan in pretreated advanced colorectal cancer...
  29. pmc Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines
    Jeet Gandhi
    Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America
    PLoS ONE 4:e4576. 2009
    ..Mutations of EGFR (mEGFR) and copy number gains (CNGs) of EGFR (gEGFR) and HER2 (gHER2) have been reported to predict for TKI response. Mutations in KRAS (mKRAS) are associated with primary resistance to TKIs...
  30. doi A comparison of EGFR and KRAS status in primary lung carcinoma and matched metastases
    Sara E Monaco
    Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA
    Hum Pathol 41:94-102. 2010
    Epidermal growth factor receptor (EGFR) and v-Ki-ras 2 (KRAS; viral Kirsten rat sacoma 2 oncogene homolog) oncogenes are predictors of response to EGFR-targeted therapy in lung carcinomas...
  31. ncbi Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma
    Gad Singer
    Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    J Natl Cancer Inst 95:484-6. 2003
    ..The apparent restriction of these BRAF and KRAS mutations to low-grade serous ovarian carcinoma and its precursors suggests that low-grade and high-grade ovarian serous carcinomas develop through independent pathways...
  32. doi Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial
    Jean Yves Douillard
    M D Anderson Cancer Center, Thoracic Head and Neck Medical Oncology, Box 432, 1515 Holcombe Blvd, Houston, TX 77401, USA
    J Clin Oncol 28:744-52. 2010
    ....
  33. doi Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab
    Wendy De Roock
    Center for Human Genetics, University of Leuven, Leuven, Belgium
    JAMA 304:1812-20. 2010
    ..Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab...
  34. pmc Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome
    Nathan T Ihle
    Department of Experimental Therapeutics, The Hamon Center for Therapeutic Oncology Research and Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
    J Natl Cancer Inst 104:228-39. 2012
    Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) play a critical role in cancer cell growth and resistance to therapy. Most mutations occur at codons 12 and 13...
  35. pmc The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer
    V Eklöf
    Department of Medical Biosciences Pathology, Umea University, SE 901 85 Umea, Sweden
    Br J Cancer 108:2153-63. 2013
    ..Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC...
  36. ncbi Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient
    E Santos
    Science 223:661-4. 1984
    ..alteration, a guanine-to-cytosine transversion, is responsible for the acquisition of malignant properties by K-ras genes of two human tumor cell lines established from carcinomas of the bladder (A1698) and lung (A2182)...
  37. pmc Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies
    Michael Steckel
    Signal Transduction, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Cell Res 22:1227-45. 2012
    Oncogenic mutations in RAS genes are very common in human cancer, resulting in cells with well-characterized selective advantages, but also less well-understood vulnerabilities...
  38. doi Genetic aberrations in primary esophageal melanomas: molecular analysis of c-KIT, PDGFR, KRAS, NRAS and BRAF in a series of 10 cases
    Rupert Langer
    Institute of Pathology, Technische Universitat Munchen, Munchen, Germany
    Mod Pathol 24:495-501. 2011
    ..We conclude that molecular analysis can identify targets for a specific therapy such as tyrosin kinase inhibitors as additional treatment option in these highly malignant tumors...
  39. pmc Identification of mutant K-Ras-dependent phenotypes using a panel of isogenic cell lines
    Steffan Vartanian
    Department of Discovery Oncology, Genentech Inc, South San Francisco, California 94080, USA
    J Biol Chem 288:2403-13. 2013
    To assess the consequences of endogenous mutant K-Ras, we analyzed the signaling and biological properties of a small panel of isogenic cell lines...
  40. doi Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC
    Anne M J Gilsing
    Department of Epidemiology and
    Carcinogenesis 34:2757-66. 2013
    ..dietary heme iron intake and risk of CRC with mutations in APC (adenomatous polyposis coli) and KRAS (Kirsten ras) and P53 overexpression in the Netherlands Cohort Study. After 7.3 years of follow-up, excluding the first 2...
  41. doi A let-7 microRNA SNP in the KRAS 3'UTR is prognostic in early-stage colorectal cancer
    Kim M Smits
    Departments of Pathology and Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
    Clin Cancer Res 17:7723-31. 2011
    ..Effects in early-stage CRC are however unknown. We studied KRAS-LCS6 genotype, hypothesizing that it might identify early-stage cases with a poor prognosis, and could potentially be used in therapy decision-making...
  42. pmc Oncogenic K-Ras and loss of Smad4 mediate invasion by activating an EGFR/NF-κB Axis that induces expression of MMP9 and uPA in human pancreas progenitor cells
    Alakesh Bera
    Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America
    PLoS ONE 8:e82282. 2013
    Activating K-Ras mutations and inactivating mutations of Smad4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC)...
  43. doi A let-7 microRNA-binding site polymorphism in 3'-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy
    W Zhang
    Division of Medical Oncology, University of Southern California Norris COomprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA
    Ann Oncol 22:104-9. 2011
    ..We tested the hypothesis whether this polymorphism may be associated with clinical outcome in KRAS wild-type (KRASwt) mCRC patients treated with cetuximab monotherapy...
  44. doi KRAS gene mutations in lung cancer: particulars established and issues unresolved
    Koji Okudela
    Department of Pathology, Yokohama City University Graduate School of Medicine, Kanazawa Ku, Yokohama, Japan
    Pathol Int 60:651-60. 2010
    ..The KRAS gene, belonging to the RAS gene family, encodes a membrane-bound 21-kd guanosine triphosphate (GTP)-binding protein...
  45. pmc The oncogenic kinase Pim-1 is modulated by K-Ras signaling and mediates transformed growth and radioresistance in human pancreatic ductal adenocarcinoma cells
    Dapeng Xu
    Department of Biology, Cancer Research Program, JLC Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA
    Carcinogenesis 32:488-95. 2011
    ..Pim-1 is also transcriptionally induced upon oncogenic K-Ras-mediated transformation of the human pancreatic ductal epithelial (HPDE) cell model of PDAC...
  46. pmc Different metastatic pattern according to the KRAS mutational status and site-specific discordance of KRAS status in patients with colorectal cancer
    Mi Jung Kim
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
    BMC Cancer 12:347. 2012
    ..The concordance rates of the KRAS status between primary tumor sites and paired metastatic organs were also analyzed...
  47. pmc Biomarkers of benefit from cetuximab-based therapy in metastatic colorectal cancer: interaction of EGFR ligand expression with RAS/RAF, PIK3CA genotypes
    George Pentheroudakis
    Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece
    BMC Cancer 13:49. 2013
    ..We studied EGFR-axis messenger RNA (mRNA) expression and RAS, RAF, PIK3CA mutations in order to identify additional biomarkers of cetuximab efficacy.
  48. pmc Characterization of KRAS rearrangements in metastatic prostate cancer
    Xiao Song Wang
    Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Cancer Discov 1:35-43. 2011
    ..This is the first report of a gene fusion involving the Ras family, suggesting that this aberration may drive metastatic progression in a rare subset of prostate cancers.
  49. doi Potential clinical significance of a plasma-based KRAS mutation analysis in patients with advanced non-small cell lung cancer
    Shuhang Wang
    Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
    Clin Cancer Res 16:1324-30. 2010
    ..This study aims to evaluate a plasma-based KRAS mutation analysis and the clinical significance of plasma KRAS mutation as a predictive marker for tumor resistance to EGFR-TKIs in patients with NSCLC...
  50. pmc High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade
    Michael K Kiessling
    German Cancer Research Center, Heidelberg, Germany
    Blood 117:2433-40. 2011
    ..We detected oncogenic mutations for the RAS pathway in 4 of 90 samples...
  51. doi A systematic review and meta-analysis of KRAS status as the determinant of response to anti-EGFR antibodies and the impact of partner chemotherapy in metastatic colorectal cancer
    Barbara Ann Adelstein
    Lowy Cancer Centre and Prince of Wales Clinical School, Faculty of Medicine, University of NSW, NSW 2052, Australia
    Eur J Cancer 47:1343-54. 2011
    ..This study systematically reviewed the evidence for KRAS mutation status as a treatment effect modifier of response to anti-EGFR antibodies and the influence of partner chemotherapy...
  52. doi KRAS mutation correlates with accelerated metastatic progression in patients with colorectal liver metastases
    Garrett M Nash
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Ann Surg Oncol 17:572-8. 2010
    ..To examine more directly whether KRAS mutations are associated with accelerated metastatic progression, we evaluated KRAS mutation as well as Ki-67 expression in patients with colorectal liver metastases not treated with cetuximab...
  53. pmc Prevalence of the variant allele rs61764370 T>G in the 3'UTR of KRAS among Dutch BRCA1, BRCA2 and non-BRCA1/BRCA2 breast cancer families
    Antoinette Hollestelle
    Department of Medical Oncology, Josephine Nefkens Institute and Daniel den Hoed Cancer Center, Erasmus University Medical Center, Rotterdam, The Netherlands
    Breast Cancer Res Treat 128:79-84. 2011
    ..Importantly, results from the current study suggest that KRAS-variant frequencies might be increased among BRCA1 carriers, but solid proof requires confirmation in a larger cohort of BRCA1 carriers...
  54. doi KRAS and BRAF mutations in patients with rectal cancer treated with preoperative chemoradiotherapy
    Jochen Gaedcke
    Department of General and Visceral Surgery, University Medical Center, Georg August University Gottingen, Robert Koch Str 40, 37075 Gottingen, Germany
    Radiother Oncol 94:76-81. 2010
    ..KRAS and BRAF are mutated in 35% and 10% of colorectal cancers, respectively. However, data specifically for locally advanced rectal cancers are scarce, and the frequency of KRAS mutations in codons 61 and 146 remains to be established...
  55. doi Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma
    Jenifer L Marks
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Thorac Oncol 3:111-6. 2008
    ..Whether EGFR and KRAS mutations also have an impact on survival in patients who undergo lung resection for curative intent in the absence of targeted therapy has not been established...
  56. doi KRAS mutation status in primary nonsmall cell lung cancer and matched metastases
    Alexis B Cortot
    Department of Pulmonary Diseases, Lyon Sud Hospital Center, Claude Bernard University, Lyon, France
    Cancer 116:2682-7. 2010
    The objective of this study was to determine whether the mutation status of the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) differed between primary tumors and matched distant ..
  57. pmc NRAS mutations are rare in colorectal cancer
    Natsumi Irahara
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
    Diagn Mol Pathol 19:157-63. 2010
    Activating mutations in members of the RAS oncogene family (KRAS, HRAS, and NRAS) have been found in a variety of human malignancies, suggesting a dominant role in carcinogenesis...
  58. pmc KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer
    F Loupakis
    Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Istituto Toscano Tumori and Department of Oncology, Transplantes and New Technologies in Medicine, University of Pisa, Via Roma 67 56126 Pisa, Italy
    Br J Cancer 101:715-21. 2009
    ..KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E mutation has been associated with resistance. Additional KRAS mutations are described in CRC...
  59. pmc Clinical relevance of KRAS in human cancers
    Sylwia Jancík
    Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 775 20 Olomouc, Czech Republic
    J Biomed Biotechnol 2010:150960. 2010
    The KRAS gene (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is an oncogene that encodes a small GTPase transductor protein called KRAS...
  60. pmc Deregulated miRNAs in hereditary breast cancer revealed a role for miR-30c in regulating KRAS oncogene
    Miljana Tanic
    Human Genetics Group, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    PLoS ONE 7:e38847. 2012
    ..In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling...
  61. pmc Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK
    Alice T Shaw
    Department of Pathology, Massachusetts General Hospital, Warren 501c, 55 Fruit St, Boston, MA 02114, USA
    J Clin Oncol 27:4247-53. 2009
    ..To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK...
  62. ncbi KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer
    Astrid Lievre
    Universite Paris Descartes, Institut National de la Sante et de la Recherche Medicale UMR 775, Paris, France
    Cancer Res 66:3992-5. 2006
    ..The EGFR amplification, which is not as frequent as initially reported, is also associated with response to this treatment...
  63. pmc A 3'-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis
    Trupti Paranjape
    Department of Therapeutic Radiology, Yale University, New Haven, CT 06880, USA
    Lancet Oncol 12:377-86. 2011
    ..We aimed to investigate the association of this KRAS variant with breast cancer and tumour biology...
  64. pmc Mutations in APC, Kirsten-ras, and p53--alternative genetic pathways to colorectal cancer
    Gillian Smith
    Cancer Research United Kingdom Molecular Pharmacology Unit, Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom
    Proc Natl Acad Sci U S A 99:9433-8. 2002
    ..the sequential accumulation of mutations in specific genes, including adenomatous polyposis coli (APC), Kirsten-ras (K-ras), and p53, drives the transition from healthy colonic epithelia through increasingly dysplastic adenoma to ..
  65. ncbi The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis
    Reiko Dehari
    Department of Pathology, Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA
    Am J Surg Pathol 31:1007-12. 2007
    ..The above results suggest that the majority of high-grade and low-grade carcinomas develop independently but in rare cases, a high-grade serous carcinoma may arise from an atypical proliferative serous (borderline) tumor...
  66. doi The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer
    Herbert I Hurwitz
    Duke University Medical Center, Division of Hematology and Oncology, Durham, NC 27710 0001, USA
    Oncologist 14:22-8. 2009
    Mutations of the K-ras gene were identified as a prognostic marker in metastatic colorectal cancer (mCRC)...
  67. ncbi Mutant KRAS, chromosomal instability and prognosis in colorectal cancer
    Patrizio Castagnola
    National Institute for Cancer Research, Largo R Benzi, 10, 16132 Genoa, Italy
    Biochim Biophys Acta 1756:115-25. 2005
    The RAS gene family provides a global effect on gene expression by encoding small GTP-binding proteins which act as molecular switches connecting extracellular signals with nuclear transcription factors...
  68. pmc Cigarette smoking and colorectal cancer risk by KRAS mutation status among older women
    N J Samadder
    Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Am J Gastroenterol 107:782-9. 2012
    ..In this study, we evaluated associations between cigarette smoking and CRC risk stratified by KRAS mutation status, using data and tissue resources from the Iowa Women's Health Study (IWHS)...
  69. pmc The KRAS-variant is associated with risk of developing double primary breast and ovarian cancer
    Robert Pilarski
    The Ohio State University Comprehensive Cancer Center and Department of Internal Medicine, Columbus, Ohio, United States of America
    PLoS ONE 7:e37891. 2012
    ....
  70. doi Diverging gain-of-function mechanisms of two novel KRAS mutations associated with Noonan and cardio-facio-cutaneous syndromes
    Ion C Cirstea
    Institute of Biochemistry and Molecular Biology II, Heinrich Heine University, Dusseldorf 40225, Germany
    Hum Mol Genet 22:262-70. 2013
    Activating somatic and germline mutations of closely related RAS genes (H, K, N) have been found in various types of cancer and in patients with developmental disorders, respectively...
  71. doi Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinomas
    Tetsukan Woo
    Division of Thoracic Surgery, Kanagawa Prefectural Cardiovascular and Respiratory Center Hospital, Yokohama, Japan
    Lung Cancer 65:355-62. 2009
    ..5% vs. 37.2% for stage II NSCLC, p=0.577). The combined use of KRAS status and Ki-67 expression level could be an excellent prognostic marker to predict the post-operative recurrence of stage I ADC...
  72. doi Prognostic significance of alterations in KRAS isoforms KRAS-4A/4B and KRAS mutations in colorectal carcinoma
    Jehad Abubaker
    Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
    J Pathol 219:435-45. 2009
    Somatic KRAS mutation is an early well-known event in colorectal carcinogenesis but a complete understanding of RAS function and dysfunction in colorectal cancer is still to come...
  73. pmc Two multiplex assays that simultaneously identify 22 possible mutation sites in the KRAS, BRAF, NRAS and PIK3CA genes
    Irene Lurkin
    Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands
    PLoS ONE 5:e8802. 2010
    ..In addition, these assays are cheaper and easier to interpret. The assays may also be of use for selection of patients with other tumor types...
  74. doi KRAS mutations in lung cancer
    Niki Karachaliou
    Pangaea Biotech, Dexeus University Institute, Barcelona, Spain
    Clin Lung Cancer 14:205-14. 2013
    ....
  75. doi The proto-oncogene KRAS and BRAF profiles and some clinical characteristics in colorectal cancer in the Turkish population
    Filiz Ozen
    Department of Medical Genetics, Medeniyet University Göztepe Training and Research Hospital, Istanbul, Turkey
    Genet Test Mol Biomarkers 17:135-9. 2013
    ..The aim of the current study was to investigate the prevalence and predictive significance of the KRAS and BRAF mutations in Turkish patients with colorectal cancer (CRC)...
  76. ncbi Structural differences between valine-12 and aspartate-12 Ras proteins may modify carcinoma aggression
    F Al-Mulla
    The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK
    J Pathol 187:433-8. 1999
    Recent evidence associates the codon 12 valine-for-glycine (G12V) mutant Ki-Ras protein with higher stage and increased lethality of colorectal carcinomas, while the codon 12 aspartate-for-glycine (G12D) Ras mutation shows no such ..
  77. ncbi Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome
    Tetsuya Niihori
    Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
    Nat Genet 38:294-6. 2006
    ..CFC, we identified two heterozygous KRAS mutations in three individuals and eight BRAF mutations in 16 individuals, suggesting that dysregulation of the RAS-RAF-ERK pathway is a common molecular basis for the three related disorders.
  78. ncbi Oncogenic KRAS provides a uniquely powerful and variable oncogenic contribution among RAS family members in the colonic epithelium
    Jeffrey W Keller
    Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    J Cell Physiol 210:740-9. 2007
    Activating mutations of the RAS family of small GTPases are among the most common genetic events in human tumorigenesis...
  79. ncbi Origin and prognostic value of circulating KRAS mutations in lung cancer patients
    O Gautschi
    University of California Davis Cancer Center, 4501 X Street, Sacramento, CA 95817, USA
    Cancer Lett 254:265-73. 2007
    ..These results support the notion that circulating KRAS mutations originate from tumors and are prognostically relevant in lung cancer...
  80. pmc Expression of oncogenic K-ras and loss of Smad4 cooperate to induce the expression of EGFR and to promote invasion of immortalized human pancreas ductal cells
    Shujie Zhao
    Department of Medicine, Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX, USA
    Int J Cancer 127:2076-87. 2010
    Activating mutation of K-ras and inactivation of DPC4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC)...
  81. doi Mutation pattern of KRAS and BRAF oncogenes in colorectal cancer patients
    I Rako
    Department of Laboratory Diagnostics, Division of Molecular Diagnostics, University Hospital Center Zagrab, Croatia
    Neoplasma 59:376-83. 2012
    ..Prospective studies are to be continued in order to determine whether these mutations contribute to progression of colorectal cancer...
  82. pmc Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia
    Grazia Palomba
    Istituto di Chimica Biomolecolare, CNR, Sassari, Italy
    J Transl Med 10:178. 2012
    ..In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia...
  83. pmc Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers
    Snjezana Dogan
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Clin Cancer Res 18:6169-77. 2012
    ..The molecular epidemiology of most EGFR and KRAS mutations in lung cancer remains unclear...
  84. pmc EGFR and K-ras gene mutation status in squamous cell anal carcinoma: a role for concurrent radiation and EGFR inhibitors?
    A Paliga
    Faculty of Medicine, McGill University, Montreal, Quebec, Canada H3G 1Y6
    Br J Cancer 107:1864-8. 2012
    ..We wanted to assess EGFR and Kirsten-ras (K-ras) status in SCAC to see whether it compares with SccH&N.
  85. doi [Correlation between KRAS mutations and clinicopathologic features in colorectal carcinomas]
    Jie Gao
    Department of Pathology, Chinese Academy of Medical Sciences, Beijing, China
    Zhonghua Bing Li Xue Za Zhi 41:595-8. 2012
    ..To investigate mutations of KRAS gene and clinicopathological characteristics of colorectal carcinomas (CRC) in Chinese...
  86. pmc Computational analysis of KRAS mutations: implications for different effects on the KRAS p.G12D and p.G13D mutations
    Chih Chieh Chen
    Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan
    PLoS ONE 8:e55793. 2013
    ..The aim of the current study was to perform computational analysis to investigate the structural implications of the underlying mutations caused by c.38G>A (p.G13D) on protein conformation...
  87. pmc Simultaneous identification of 36 mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA in a single reaction by multiplex assay kit
    Hideaki Bando
    Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6 5 1 Kashiwanoha, Kashiwa, Chiba 277 8577, Japan
    BMC Cancer 13:405. 2013
    ..We developed a novel multiplex kit detecting 36 mutations in KRAS codons 61 and 146, BRAF, NRAS, and PIK3CA using Luminex (xMAP) assay in a single reaction...
  88. doi Mutual exclusiveness between PIK3CA and KRAS mutations in endometrial carcinoma
    S Kang
    Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea
    Int J Gynecol Cancer 18:1339-43. 2008
    ..PIK3CA was frequently mutated in endometrial cancers. KRAS and PIK3CA mutations are inversely correlated, suggesting that genetic alterations of KRAS and PIK3CA may play equivalent roles in endometrial carcinogenesis...
  89. doi PIK3CA mutations predict local recurrences in rectal cancer patients
    Youji He
    Departments of Experimental Therapy, Pathology, and Radiotherapy, Netherlands Cancer Institute, Amsterdam, The Netherlands
    Clin Cancer Res 15:6956-62. 2009
    ..In this study, we aim to determine the mutation frequencies of PIK3CA, KRAS, and BRAF and to investigate whether a mutation may be used as a prognostic parameter in rectal cancer patients...
  90. doi Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer: National Cancer Institute of Canada Clinical Trials Group Study PA.3
    Gilda da Cunha Santos
    Department of Pathology, University Health Network, Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada
    Cancer 116:5599-607. 2010
    ..Mutation status of the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and EGFR gene copy number (GCN) were evaluated as predictive markers in 26% of patients ..
  91. doi Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers
    Shin Yup Lee
    Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
    J Thorac Oncol 5:1734-40. 2010
    ..We searched for mutations of EGFR pathway genes in non-small cell lung cancers (NSCLCs) and analyzed their relationship with clinicopathologic features...
  92. doi Rapid detection of low-abundance K-ras mutation in stools of colorectal cancer patients using chip-based temperature gradient capillary electrophoresis
    Huidan Zhang
    Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China
    Lab Invest 91:788-98. 2011
    Mutant K-ras provides an independent negative predictive marker for epidermal growth factor receptor (EGFR)-targeted therapy in colorectal cancers (CRCs)...
  93. doi Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status
    Dominik P Modest
    Medical Department III, Hospital of the University, University of Munich, Germany
    Anticancer Drugs 22:913-8. 2011
    ..Compared with KRAS codon 12 mutations, codon 13-mutated mCRC presents as a more aggressive disease frequently associated with local and distant metastases at first diagnosis...
  94. doi Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients treated with first-line gemcitabine-based chemotherapy
    Seung Tae Kim
    Division of Hematology Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon dong Gangnam gu, Seoul 135 710, Korea
    Mol Cancer Ther 10:1993-9. 2011
    ..0 vs. 7.0 months; P = 0.121). These results need to be further explored in upcoming prospective studies to provide a rationale for personalized medicine in pancreatic cancer...
  95. pmc KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer
    Chen Mao
    Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, People s Republic of China
    PLoS ONE 7:e36653. 2012
    ..To investigate the frequency and relationship of the KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer (CRC)...
  96. pmc Growth inhibitory effect of wild-type Kras2 gene on a colonic adenocarcinoma cell line
    Hong Li
    Inpatient Department of Medical Health Center, Chinese PLA General Hospital, Beijing 100853, China
    World J Gastroenterol 13:934-8. 2007
    To observe the growth inhibitory effect of wild-type Kras2 gene on a colonic adenocarcinoma cell line Caco-2.
  97. doi KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: biological and clinical implications
    Antoine Italiano
    Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice, France
    Ann Surg Oncol 17:1429-34. 2010
    ..The question of primary resistance to anti-EGFR treatment as a result of the presence of KRAS or BRAF mutations only in metastases has been raised but not resolved...
  98. doi Cycleave polymerase chain reaction method is practically applicable for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)/V-raf murine sarcoma viral oncogene homolog B1 (BRAF) genotyping in colorectal cancer
    Tomoya Yokota
    Department of Clinical Oncology, Aichi Cancer Center Hospital, Kanokoden, Chikusa ku, Nagoya, Japan
    Transl Res 156:98-105. 2010
    Activating V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutations are important predictive markers for antiepidermal growth factor receptor chemotherapy in ..
  99. doi A brief retrospective report on the feasibility of epidermal growth factor receptor and KRAS mutation analysis in transesophageal ultrasound- and endobronchial ultrasound-guided fine needle cytological aspirates
    Olga C J Schuurbiers
    Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    J Thorac Oncol 5:1664-7. 2010
    ..In this study, we aimed to investigate the yield and applicability of molecular testing for KRAS and EGFR mutations in cytologic specimens obtained by EUS or endobronchial ultrasound (EBUS)-guided fine needle aspiration (FNA)...
  100. pmc Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models
    Silvestre Vicent
    Cancer Biology Program, Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
    J Clin Invest 120:3940-52. 2010
    ..the mechanisms regulating these 2 drastically distinct outcomes would help identify novel therapeutic approaches in RAS-driven cancers...
  101. ncbi APC, K-ras, and p53 gene mutations in colorectal cancer patients: correlation to clinicopathologic features and postoperative surveillance
    Jan Sing Hsieh
    Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan
    Am Surg 71:336-43. 2005
    ..accumulation of mutations in specific cancer-related genes, including adenomatous polyposis coli (APC), K-ras, and p53, drives the transition from normal epithelium through increasing adenomatous dysplasia to colorectal ..

Research Grants85

  1. MARK REID PHILIPS; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): Of the three ras genes, kras is most frequently mutated in human cancer...
  2. FREDERICK DEECHEN TSAI; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Ras oncogenes are the most frequently mutated in human cancer...
  3. Christopher M Counter; Fiscal Year: 2016
    ..Since oncogenic Ras can induce a senescent growth arrest in normal cells, we hypothesize that KRas is expressed in a very narrow range ..
  4. Immune Mechanisms of HCV Persistence and Pathogenesis
    Jiaren Sun; Fiscal Year: 2012
    ..2) To examine whether HCV nonstructural (NS) proteins, especially NS3, interfere with the host antiviral responses leading to viral persistence, we will generate mice conditionally ..
  5. Brett D Lindenbach; Fiscal Year: 2016
    ..To address these issues, we are determining how the HCV NS2 and NS3-4A proteins contribute to virus assembly...
  6. Dendritic cell targeted hepatitis c virus immunotherapy
    Tyler Curiel; Fiscal Year: 2003
    ..The objective of this proposal is to develop a novel vaccine strategy targeting the HCV nonstructural protein 3 (NS3) directly to DC subsets, e.g., Langerhans Cells (LCs)...
  7. Novel Strategy for HCV NS3 Inhibitor Discovery
    Steven Ogata; Fiscal Year: 2001
    ..The nonstructural protein 3 (NS3) of HCV is a multi-functional enzyme in the replication cycle of the virus and requires NS4A as cofactor for ..
  8. A Small Molecule to Activate Cetuximab to Kill K-RAS Mutant Colorectal Tumors
    Barry Jones; Fiscal Year: 2013
    ..If the STTR Phase I study is successful, IND-enabling studies and the initiation of a phase 1 clinical trial of ARI-4175 will be proposed for STTR Phase II. ..
  9. Nancy R Zhang; Fiscal Year: 2015
    ..These studies have implications for generation of novel diagnostic and therapeutic strategies for colon cancer. ..
  10. Warren N Schmidt; Fiscal Year: 2016
    ..Metalloporphyrins (MPs) such as heme and heme oxidation products such as biliverdin potently inhibit HCV NS3/4a protease...
  11. Elucidating the Mechanism of Novel Dengue Antivirals
    Stanley Watowich; Fiscal Year: 2009
    ..to combat this high-priority and widespread pathogen, we used "virtual screening" to discover putative DEN2V NS3 protease inhibitors...
  12. Priyamvada Rai; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Approximately 25% of all tumor types sustain oncogenic RAS mutations...
  13. Channing J Der; Fiscal Year: 2016
    ..Thus, it is widely believed that anti-K-Ras targeted therapies will have a significant clinical benefit for the PDAC patient...
  14. Antiviral potential of helicase inhibitors
    David N Frick; Fiscal Year: 2012
    ..to be developed are needed as part of an ongoing collaborative hypothesis-driven research project to develop HCV NS3 helicase inhibitors as chemical probes to facilitate basic science and for drug development...
  15. Garth Powis; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The RAS oncogene is the most elusive cancer therapy target yet identified...
  16. Role of HCV p7 and NS2 in infectious virus production
    Charles M Rice; Fiscal Year: 2012
    ..required for HCV RNA replication other than the NS2-3 protease-mediated cleavage to liberate the N-terminus of the NS3 serine protease/helicase...
  17. YPE PETER DE JONG; Fiscal Year: 2015
    ..At the earliest steps of viral sensing, the HCV NS3-4A protease cleaves two adaptor molecules, MAVS and TRIF, rendering both RIG-I and TLR3 pathways ineffective and ..
  18. EXPRESSION OF THE HUMAN C-K-RAS GENE
    Manuel Perucho; Fiscal Year: 1993
    ..applicant's abstract): During the investigators's studies on the role of somatic mutational activation of the c-K-ras gene in human colo-rectal tumorigenesis, they have found that differences in the molecular nature of mutations ..
  19. Innate Control of Hepatitis C Virus Infection: Antiviral and Evasion Mechanisms
    FRANCIS CHISARI; Fiscal Year: 2009
    ..Using that model we have recently shown that that the viral NS3/4A protease blocks double stranded (ds) RNA signaling and type 1 interferon (IFN) induction by cleaving a key ..
  20. Structure and function of the HCV RNA replicase
    Charles M Rice; Fiscal Year: 2013
    ..We then aim to elucidate the roles of two important but enigmatic viral proteins, the NS3 helicase and NS5A...
  21. Charles M Rice; Fiscal Year: 2016
    ..Addition of direct-acting antivirals (DAAs) targeting the HCV NS3/4A protease increases SVR rates to 68-75% in previously untreated patients, but such regimens still suffer from the ..
  22. DJADE IBRAHIM SOUMANA; Fiscal Year: 2015
    ..That being said, I propose that by understanding the differences in substrate recognition of the most divergent HCV NS3/4A protease, we can get one step closer to designing an inhibitor that satisfies two major properties: 1) the ..
  23. Endocrine Targets for Prevention of Lung Cancer
    Robert M Bigsby; Fiscal Year: 2012
    ..These minimal studies will pave the way for testing receptor specific estrogen antagonists and additional PR-specific antagonists in prevention of tumor growth and progression in the lung. ..
  24. Navdeep S Chandel; Fiscal Year: 2015
    ....
  25. Cx43 phosphorylation modulates Kras mediated pancreas cancer progression
    Paul D Lampe; Fiscal Year: 2012
    ..Since drugs that affect Cx43 activity and gap junctional communication are under development, understanding how these factors affect progression could ultimately lead to better treatment of this lethal disease. ..
  26. Effect of high fat diet on pancreatic cancer in IKKa deficient mice
    Ning Li; Fiscal Year: 2013
    ..b>KRAS2 mutational activation is an early event found in 90% of PanIN lesions and is followed by loss of different tumor ..
  27. Phenotyping pain in a mouse model of pancreatic cancer
    Brian M Davis; Fiscal Year: 2012
    ..b) Documenting changes in pancreatic innervation for growth factor dependent afferent fibers during the course of PDAC. ..
  28. George Miller; Fiscal Year: 2016
    ....
  29. Dysregulation of TGF Beta Action Pancreatic Cancer
    Murray Korc; Fiscal Year: 2012
    ..This proposal aims to provide an improved understanding of the biological causes that contribute to this disease aggressiveness, with the ultimate goal of devising better diagnostic and therapeutic strategies. ..
  30. Identification and therapeutic application of miRNA-drivers in lung cancer
    ANDREA LYNN KASINSKI; Fiscal Year: 2013
    ..The identification of miRNAs and targeted-therapies to perturb miRNA imbalance that occurs in cancer is invaluable to the fields of cancer and miRNA biology, and has direct clinical application. ..
  31. Martin McMahon; Fiscal Year: 2016
    ..However, the immediate objective of this proposal is to explore the role of the Ras-activated RAF->MEK->ERK MAP kinase signal transduction pathway in the initiation, progression and therapy of ..
  32. Alec Kimmelman; Fiscal Year: 2015
    ....
  33. Chemoprevention of Lung Cancer with Anti-tumor B
    Ming You; Fiscal Year: 2010
    ..and tumor load, ATB exhibited an enhanced inhibitory effect in animals harboring all three genetic alterations (Kras2, p53, and Ink4A)...
  34. Gail L Matters; Fiscal Year: 2016
    ..Our long term goal is to develop novel effective strategies to improve therapy and survival of patients with this devastating malignancy. ..
  35. Advancing clemizole for hepatitis C: towards a pre-IND package
    Jeffrey S Glenn; Fiscal Year: 2010
    ..in the liver (>100 fold plasma levels), demonstrates dramatic in vitro synergy with SCH503034, an HCV NS3 protease inhibitor in advanced clinical development, and presumably due to its unique bi-partitie target appears to ..
  36. CYRIL HENRI BENES; Fiscal Year: 2016
    ..PROJECT SUMMARY (See Instructions) : The goal for this renewal application is to gain in-(depth knowledge of PI3K and RAS-MAPK signaling with cooperating pathways governing pancreatic ductal adenocarcinoma (PDAC) to guide clinical trials ..
  37. Sensitized screen to identify cooperating genes involved in pancreatic cancer
    Arthur M Buchberg; Fiscal Year: 2010
    ..The identification of these genes would provide new biomarkers with which to monitor the development of pancreatic cancer in humans as well as to identify molecular pathways with which to target new therapeutic regimens. ..
  38. Jie Wu; Fiscal Year: 2016
    ..Moreover, the novel Cre recombinase-mediated cassette exchange-enable transgenic mice characterized in this study will give the research community an important resource to accelerate mouse model studies of human diseases. ..
  39. VALERY G KRASNOPEROV; Fiscal Year: 2014
    ..These results will guide us to identify the pharmacodynamic biomarker of sEphB4-HSA, which will be very useful in the evaluation of patient responses in the clinic. ..
  40. Michael Karin; Fiscal Year: 2016
    ..The completion of these studies will result in a much better understanding of the molecular etiology of PanCa and may lead to new strategies for blocking the progression of precursor lesions to invasive PDAC. ..
  41. BRIAN JOSEPH QUATTROCHI; Fiscal Year: 2015
    ....
  42. Pier Paolo Pandolfi; Fiscal Year: 2014
    ..and DOK-3 as lung tumor suppressors, and we further hypothesize that they are negative regulators of oncogenic EGFR-RAS signaling...
  43. Yi Sun; Fiscal Year: 2014
    ..Our work is, therefore, highly innovative and of significant impact with translational value. ..
  44. Marc Ladanyi; Fiscal Year: 2016
    ....
  45. MICHAEL ALEXANDER BADGLEY; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): RAS is among the most potent oncogenes in the human genome and is mutated in over one in four of all human cancers [1]...
  46. Non-Cell Autonomous Functions of N-cadherin in KRas-driven Preneoplastic Lesions
    ERIN MARIE BEKES; Fiscal Year: 2013
    ..abstract_text> ..
  47. Jeffrey S Glenn; Fiscal Year: 2014
    ..H1 antihistamine-clemizole-potently inhibits NS4B RNA binding and exhibits dramatic in vitro synergy with the HCV NS3 protease inhibitor SCH503034...
  48. Markers of Early Pancreatic Cancer
    Michael G Goggins; Fiscal Year: 2010
    ..2B: To demonstrate the diagnostic utility of LigAmp to detect and quantify KRAS2 and BRAF mutations in pancreatic juice and in serum from patients with pancreatic cancer and appropriate controls...
  49. William Y Kim; Fiscal Year: 2014
    ....
  50. Celia A Schiffer; Fiscal Year: 2016
    ..New drugs targeting the viral protein, NS3/4A, which is a bifunctional protease/helicase are in clinical trials...
  51. Jen Jen J Yeh; Fiscal Year: 2014
    ..The new nanotechnology innovations are expected to have broad applicability across multiple tumor types and benefit a large number of cancer patients with different types of malignancies. ..
  52. Mediators of Oncogenic KRAS in Lung Adenocarcinoma
    Jonathan M Kurie; Fiscal Year: 2010
    ....
  53. The Role of glypican-1 in Pancreatic Cancer Development and Progression
    CHERY ANGEL WHIPPLE; Fiscal Year: 2013
    ..These data may provide support for the efficacy of targeting GPC1 either alone or in combination with other therapeutic targets. ..
  54. GLORIA HUEI TING SU; Fiscal Year: 2015
    ..These experiments will help us better understand the mechanism of metastasis and to develop more effective target therapies for pancreatic cancer patients. ..
  55. Don X Nguyen; Fiscal Year: 2016
    ..The overall goal of our proposal may therefore shed new light into the origins of aggressive metastatic tumors, and provide insights into more accurate diagnostic modalities for lung cancer patients at risk for metastatic disease. ..
  56. Peripheral blood biopsy for molecular diagnosis of pancreatic cancer
    Sunil R Hingorani; Fiscal Year: 2013
    ..It can be reasonably hoped that the final diagnostic tool would enable clinicians to make molecular diagnoses non-invasively and monitor for minimal residual disease, disease progression, and response or resistance to treatment. ..
  57. Ki-Ras Signaling in Pancreatic Cancer: Role of a Novel Akt Regulator
    Sushovan Guha; Fiscal Year: 2013
    ..For the most part, the signaling mechanisms deregulated in response to genetic alterations in the Ki-Ras gene, and by other well- established hallmarks of pancreatic carcinogenesis, are still incompletely understood...
  58. Stephen F Konieczny; Fiscal Year: 2016
    ..S.) and will direct future approaches aimed at testing new biomarkers and developing improved diagnostic and therapeutic tools to successfully treat patients suffering from this deadly disease. ..
  59. Phosphatidylinositol 3-kinase and prevention of pancreatic cancer
    Richard Z Lin; Fiscal Year: 2013
    ..Successful completion of our animal studies should lead to investigation of natural and synthetic PI3K inhibitors as a chemopreventive intervention for pancreatic cancer in humans. ..
  60. Development of Antiviral Therapeutics for Dengue: Inhibitors of Viral Protease
    Radhakrishnan Padmanabhan; Fiscal Year: 2010
    ..In aim 1, we propose to identify new inhibitors of the viral NS3 protease and compounds that block NS3/NS5 interaction by high throughput screening (HTS) and by virtual screening...
  61. Mechanisms of Lung Cancer
    KATHRYN VICTORIA TORMOS; Fiscal Year: 2010
    ..produced, in vivo lung adenocarcinomas and provides a platform to study the mechanisms underlying oncogenic Ras driven lung tumorigenesis...
  62. Mouse Model for Human Pancreatic Ductal Adenocarcinoma
    Gloria Su; Fiscal Year: 2009
    ..PHS 398/2590 (Rev. 11/07) Page Continuation Format Page ..
  63. GUIDO ERWIN MICHAEL EIBL; Fiscal Year: 2016
    ..abstract_text> ..
  64. Tikvah K Hayes; Fiscal Year: 2016
    ..As a consequence, Ras effector signaling has moved to the forefront of drug discovery...
  65. Biology and Immunology of Pancreatic Cancer Stem Cells in a Novel Mouse Model
    Edgar G Engleman; Fiscal Year: 2013
    ....
  66. Guang Yu Yang; Fiscal Year: 2016
    ....
  67. LEWIS C MURTAUGH; Fiscal Year: 2014
    ..Instead, additional stimuli synergize with RAS o promote transformation, and this synergy is first evident in ductal reprogramming of the exocrine acinar cells ..
  68. Binnaz Kucuk Staley; Fiscal Year: 2015
    ....
  69. Garth Powis; Fiscal Year: 2016
    ..Finally, we have identified and validated a novel target for small molecule drug development that will allow us to break the cycle of hypoxia and desmoplasia in pancreatic cancer. ..
  70. Mouse Model of Pancreatic Cancer Progression-Maintenance
    Nabeel Bardeesy; Fiscal Year: 2009
    ..An important component of my program will be my continued participation in a multidisciplinary consortium of pancreatic cancer researchers currently in the process of addressing a series of programmatic initiatives. ..
  71. BENJAMIN BRAUN; Fiscal Year: 2016
    ..Despite intensive study of Ras signaling, the basic mechanisms by which Ras activation causes excessive myeloid cell production and anemia in MDS/..
  72. Alan P Fields; Fiscal Year: 2016
    ....
  73. George Souroullas; Fiscal Year: 2014
    ....
  74. The Meningioma Consortium: Genome-Wide Association Study
    Elizabeth B Claus; Fiscal Year: 2013
    ..previous associations from the Tineas Capitas study of meningioma risk with variants in DNA repair genes (KRAS2, ERCC2, CCND1)...
  75. Functions of NS3 in HCV RNA Replication
    Minkyung Yi; Fiscal Year: 2006
    ..HCV NS3 encodes several important enzyme activities required for RNA replication, including protease, helicase and NTPase...
  76. Guang Yu Yang; Fiscal Year: 2016
    ....
  77. HCV NS3: Biological, Biochemical and Structural Analysis
    KEVIN RANEY; Fiscal Year: 2006
    ..b>NS3, NS4A, NS4B, NS5A, and NS5B appear to interact structurally and functionally...
  78. Ha Linh Vu; Fiscal Year: 2016
    ..Therapies that target RAS and MEK, a RAS effector, have not been clinical effective in mutant NRAS melanoma patients...
  79. NATALIA ALEKSANDR OSNA; Fiscal Year: 2016
    ..Others have demonstrated that hypomethylation leads to activation of HCV NS3/4 protease, which may potentially block host innate antiviral immunity through NS3/4a-mediated cleavage of the ..
  80. Optimization of SWCNT/siRNA complex formulation for tumor accumulation
    Lynn Kirkpatrick; Fiscal Year: 2012
    ..These critical studies will move this novel technology one step closer to full pre-clinical development and eventually to a clinical trial study. ..
  81. Identification and Analysis of Flavivirus Protease and RNA Helicase Inhibitors
    Radhakrishnan Padmanabhan; Fiscal Year: 2009
    ..Two of the nonstructural proteins, NS3 and NS5, have multiple enzyme activities that are required for the virus life cycle...
  82. FUNCTIONAL ANALYSIS OF DENGUE VIRUS ANTIGENS NS3 AND NS5
    Radhakrishnan Padmanabhan; Fiscal Year: 2003
    ..3. Two hypotheses will be tested, using site directed mutants of NS3 in the in vitro viral replicase assay and the in vivo assay of mutant genomic RNAs trans-complemented by wild type ..
  83. STRUCTURE BASED ANALYSIS OF DENGUE VIRUS SERINE PROTEASE
    Krishna Murthy; Fiscal Year: 2004
    ..of the viral polyprotein precursor in host cells is carried out by the two-component viral protease, NS2B/NS3, which plays a pivotal role in the virus life cycle...
  84. HUMAN IMMUNE RESPONSES TO YELLOW FEVER VIRUS
    Sharone Green; Fiscal Year: 2004
    ..human flavivirus, dengue, have demonstrated that CD4+ and CD8+ memory T cells are generated with the nonstructural NS3 protein as an immunodominant protein...