K-ras as a target for cancer therapy

Mutations of the BRAF gene in human cancer

2002 • 10,249 citations

Cell Signaling by Receptor Tyrosine Kinases

2010 • 7,477 citations

Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.

1997 • 5,683 citations

BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis

2004 • 3,873 citations

ras GENES

1987 • 3,818 citations

Cell Signaling by Receptor Tyrosine Kinases

2000 • 3,570 citations

RNA interference

2002 • 3,369 citations

Small GTP-Binding Proteins

2001 • 2,449 citations

Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells

1994 • 1,999 citations

Phosphatidylinositol-3-OH kinase direct target of Ras

1994 • 1,923 citations

Prevalence of ras gene mutations in human colorectal cancers

1987 • 1,866 citations

The activation of Akt/PKB signaling pathway and cell survival

2005 • 1,806 citations

Dimerization of cell surface receptors in signal transduction

1995 • 1,631 citations

Synthesis and Function of 3-Phosphorylated Inositol Lipids

2001 • 1,527 citations

FUNCTION AND REGULATION OF RAS

1993 • 1,161 citations

Stable suppression of tumorigenicity by virus-mediated RNA interference

2002 • 1,147 citations

Targeting the mitogen-activated protein kinase cascade to treat cancer

2004 • 1,093 citations

Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis.

1990 • 1,077 citations

Role of Phosphoinositide 3-OH Kinase in Cell Transformation and Control of the Actin Cytoskeleton by Ras

1997 • 1,064 citations

Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo

1999 • 970 citations

PROTEIN ISOPRENYLATION AND METHYLATION AT CARBOXYL-TERMINAL CYSTEINE RESIDUES

1992 • 885 citations

Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation.

2001 • 883 citations

Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation

1989 • 881 citations

Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study

2001 • 858 citations

Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors

2004 • 855 citations

K- and N-Ras Are Geranylgeranylated in Cells Treated with Farnesyl Protein Transferase Inhibitors

1997 • 848 citations

Blocking Oncogenic Ras Signaling for Cancer Therapy

2001 • 837 citations

Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts

1981 • 795 citations

Endogenous oncogenic K-rasG12D stimulates proliferation and widespread neoplastic and developmental defects

2004 • 780 citations

Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses.

1982 • 775 citations

Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer

2004 • 773 citations

Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product

1997 • 769 citations

PI 3-kinase, Akt and cell survival

2004 • 767 citations

The structural basis of the activation of Ras by Sos

1998 • 765 citations

Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase

2004 • 737 citations

Multicenter Phase II Study of the Oral MEK Inhibitor, CI-1040, in Patients With Advanced Non-Small-Cell Lung, Breast, Colon, and Pancreatic Cancer

2004 • 631 citations

Altered Growth of Human Colon Cancer Cell Lines Disrupted at Activated Ki- ras

1993 • 627 citations

Ras recruits Raf-1 to the plasma membrane for activation by tyrosine phosphorylation.

1995 • 609 citations

mTOR-targeted therapy of cancer with rapamycin derivatives

2005 • 607 citations

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

2004 • 602 citations

Sequence dependence of protein isoprenylation

1991 • 580 citations

Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation.

1996 • 568 citations

Detection of p53 Gene Mutations in Human Brain Tumors by Single-strand Conformation Polymorphism Analysis of Polymerase Chain Reaction Products

1991 • 556 citations

Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity.

1992 • 542 citations

Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With Cancer

2004 • 504 citations

Regulation of signal transduction and signal diversity by receptor oligomerization

1994 • 485 citations

Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro.

2001 • 463 citations

Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial

2001 • 458 citations

Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells

2003 • 445 citations

Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1

1983 • 441 citations

Structural Evidence for Feedback Activation by Ras·GTP of the Ras-Specific Nucleotide Exchange Factor SOS

2003 • 438 citations

The Ras branch of small Gtpases: Ras family members don’t fall far from the tree

2000 • 408 citations

A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines.

1995 • 393 citations

Ras Activation of the Raf Kinase: Tyrosine Kinase Recruitment of the MAP Kinase Cascade

2001 • 384 citations

ras Mutations Are Associated With Aggressive Tumor Phenotypes and Poor Prognosis in Thyroid Cancer

2003 • 365 citations

Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma (RCC)

2005 • 358 citations

Ral-GTPases mediate a distinct downstream signaling pathway from Ras that facilitates cellular transformation.

1996 • 335 citations

The epidermal growth factor.

1995 • 326 citations

Rab geranylgeranyl transferase. A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-Cys.

1992 • 323 citations

Relationship of Ki-ras mutations in colon cancers to tumor location, stage, and survival: a population-based study.

2000 • 313 citations

Human genome contains four genes homologous to transforming genes of Harvey and Kirsten murine sarcoma viruses.

1982 • 309 citations

GAP control: regulating the regulators of small GTPases

2004 • 299 citations

Structural Analysis of Autoinhibition in the Ras Activator Son of Sevenless

2004 • 291 citations

Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line.

1983 • 290 citations

Four Human Ras Homologs Differ in Their Abilities to Activate Raf-1, Induce Transformation, and Stimulate Cell Motility

1999 • 285 citations

Regulation of MAP kinase activity by peptide receptor signalling pathway: Paradigms of multiplicity

2001 • 280 citations

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma

2001 • 271 citations

Conditional expression of oncogenic K-ras from its endogenous promoter induces a myeloproliferative disease

2004 • 264 citations

Raf kinase as a target for anticancer therapeutics

2005 • 245 citations

Phase III Double-Blind Placebo-Controlled Study of Farnesyl Transferase Inhibitor R115777 in Patients With Refractory Advanced Colorectal Cancer

2004 • 234 citations

Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts

1998 • 229 citations

Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial

1996 • 229 citations

Ras GTPases: integrins' friends or foes?

2003 • 227 citations

Ras CAAX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation and p53 deletion.

1995 • 226 citations

Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase.

1990 • 222 citations

Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma

2003 • 215 citations

Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products.

1990 • 213 citations

Survival and acquired genetic alterations in colorectal cancer

1992 • 208 citations

Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity

2001 • 208 citations

Membrane Targeting of Lipid Modified Signal Transduction Proteins

2004 • 205 citations

Structure and biological activity of human homologs of the raf/mil oncogene.

1985 • 203 citations

Phase II Study of the Efficacy and Tolerability of Two Dosing Regimens of the Farnesyl Transferase Inhibitor, R115777, in Advanced Breast Cancer

2003 • 200 citations

Farnesyltransferase Inhibition Causes Morphological Reversion of ras-Transformed Cells by a Complex Mechanism That Involves Regulation of the Actin Cytoskeleton

1994 • 197 citations

In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model

2004 • 190 citations

High incidence of N and K-Ras activating mutations in multiple myeloma and primary plasma cell leukemia at diagnosis

2001 • 190 citations

Von Recklinghausen's neurofibromatosis: neurofibromatosis type 1

2003 • 189 citations

Ras and relatives—job sharing and networking keep an old family together

2002 • 185 citations

Ras activation in human breast cancer

2000 • 183 citations

Disruption of the Mouse Rce1 Gene Results in Defective Ras Processing and Mislocalization of Ras within Cells

1999 • 179 citations

Direct Interaction between Ras and the Kinase Domain of Mitogen-activated Protein Kinase Kinase Kinase (MEKK1)

1995 • 177 citations

A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells

2005 • 177 citations

RalGDS is required for tumor formation in a model of skin carcinogenesis

2005 • 174 citations

Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway

2004 • 169 citations

GTPases and T cell activation

2003 • 168 citations

Effects of the Mammalian Target of Rapamycin Inhibitor CCI-779 Used Alone or with Chemotherapy on Human Prostate Cancer Cells and Xenografts

2005 • 164 citations

Stimulation of angiogenesis by Ras proteins

2003 • 163 citations

Integrin-mediated signal transduction pathways.

1999 • 163 citations

Prevention of orthotopic human lung cancer growth by intratracheal instillation of a retroviral antisense K-ras construct.

1993 • 162 citations

Therapeutic targeting in the estrogen receptor hormonal pathway

2004 • 161 citations

K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: a population-based study in China.

2002 • 159 citations

Inhibition of Mammalian Target of Rapamycin Reverses Alveolar Epithelial Neoplasia Induced by Oncogenic K-ras

2005 • 150 citations

The importance of being K-Ras

2000 • 149 citations

High frequency of K-ras mutations in human colorectal hyperplastic polyps.

1997 • 148 citations

New aspects of integrin signaling in cancer

2000 • 147 citations

Absence of the CAAX Endoprotease Rce1: Effects on Cell Growth and Transformation

2002 • 146 citations

Farnesyl transferase inhibitors as anticancer agents

2002 • 142 citations

Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton.

1994 • 142 citations

Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A.

1994 • 139 citations

Activated ras Genes Occur in Human Actinic Keratoses, Premalignant Precursors to Squamous Cell Carcinomas

1995 • 137 citations

Novel mechanisms of RTK signal generation

1997 • 137 citations

Frequent alterations of Ras signaling pathway genes in sporadic malignant melanomas

2004 • 134 citations

Detection of c-K-ras mutations in fine needle aspirates from human pancreatic adenocarcinomas.

1990 • 132 citations

The TAO of MEKK

1998 • 132 citations

Characterization of Active Mitogen-Activated Protein Kinase in Ovarian Serous Carcinomas

2004 • 131 citations

Conditional Expression of K- ras in an Epithelial Compartment that Includes the Stem Cells Is Sufficient to Promote Squamous Cell Carcinogenesis

2004 • 130 citations

Mutations of the K-ras and p53 genes in gastric adenocarcinomas from a high-incidence region around Florence, Italy.

1995 • 128 citations

Lysophosphatidic Acid Stimulates Ovarian Cancer Cell Migration via a Ras-MEK Kinase 1 Pathway

2004 • 124 citations

MEKK1 Binds Raf-1 and the ERK2 Cascade Components

2000 • 120 citations

Membrane-targeting potentiates guanine nucleotide exchange factor CDC25 and SOS1 activation of Ras transforming activity.

1994 • 119 citations

Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I.

2002 • 119 citations

A Phase I Vaccine Trial with Peptides Reflecting ras Oncogene Mutations of Solid Tumors

1999 • 117 citations

Retroviral Vector-Mediated Transduction of K-rasAntisense RNA into Human Lung Cancer Cells Inhibits Expression of the Malignant Phenotype

1993 • 115 citations

Type and number of Ki-ras point mutations relate to stage of human colorectal cancer.

1994 • 111 citations

Inducible Activation of Oncogenic K- ras Results in Tumor Formation in the Oral Cavity

2004 • 109 citations

The CaaX Proteases, Afc1p and Rce1p, Have Overlapping but Distinct Substrate Specificities

2000 • 106 citations

A Phase I trial of h-ras antisense oligonucleotide ISIS 2503 administered as a continuous intravenous infusion in patients with advanced carcinoma

2001 • 101 citations

Survival and acquired genetic alterations in colorectal cancer

1992 • 100 citations

Final findings from a phase II, placebo-controlled, randomized discontinuation trial (RDT) of sorafenib (BAY 43–9006) in patients with advanced renal cell carcinoma (RCC)

2005 • 100 citations

Gemcitabine and ISIS-2503 for Patients With Locally Advanced or Metastatic Pancreatic Adenocarcinoma: A North Central Cancer Treatment Group Phase II Trial

2004 • 98 citations

A phase I and pharmacological study of the farnesyl protein transferase inhibitor L-778,123 in patients with solid malignancies.

2001 • 92 citations

Detection of B-RAF and N-RAS mutations in human melanoma

2005 • 91 citations

Farnesyltransferase inhibitors

2004 • 91 citations

Mutations of the ras gene product p21 that abolish guanine nucleotide binding.

1986 • 91 citations

A phase I trial of ISIS 2503, an antisense inhibitor of H-ras, in combination with gemcitabine in patients with advanced cancer.

2003 • 90 citations

Oncogenic K-ras Drives Cell Cycle Progression and Phenotypic Conversion of Primary Pancreatic Duct Epithelial Cells

2004 • 88 citations

GTPases in antigen receptor signalling

1998 • 83 citations

Prevalence and clinical significance of combined K-ras mutation and p53 aberration in pancreatic adenocarcinoma

1997 • 82 citations

Identification of the Anti-proliferative Protein Tob as a MAPK Substrate

2002 • 80 citations

Functional Analysis of a Phosphatidic Acid Binding Domain in Human Raf-1 Kinase

2003 • 79 citations

Molecular approach to breast cancer treatment

2004 • 78 citations

Antisense-fos RNA causes partial reversion of the transformed phenotypes induced by the c-Ha-ras oncogene.

1990 • 77 citations

Ki-ras mutations and prognosis in colorectal cancer

1998 • 77 citations

Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice.

1993 • 74 citations

Mutation-Selective Tumor Remission with Ras-Targeted, Whole Yeast-Based Immunotherapy

2004 • 73 citations

Antisense Oligonucleotides Demonstrate a Dominant Role of c-Ki-RAS Proteins in Regulating the Proliferation of Diploid Human Fibroblasts

1996 • 73 citations

Polylysine domain of K-ras 4B protein is crucial for malignant transformation.

1994 • 73 citations

K-ras mutations in nonmucinous ovarian epithelial tumors: a molecular analysis and clinicopathologic study of 144 patients.

1998 • 71 citations

Lysophosphatidic Acid Promotes Survival and Differentiation of Rat Schwann Cells

2003 • 71 citations

Farnesyltransferase Inhibitors

2001 • 70 citations

Specific Ki‐ras codon 61 mutations may determine the development of urethan‐induced mouse lung adenomas or adenocarcinomas

1990 • 65 citations

Roles of Phosphatidylinositol 3′-Kinase and Mammalian Target of Rapamycin/p70 Ribosomal Protein S6 Kinase in K-Ras-Mediated Transformation of Intestinal Epithelial Cells

2004 • 64 citations

CD8+T cells from a patient with colon carcinoma, specific for a mutant p21-Ras-derived peptide (GLY13?ASP), are cytotoxic towards a carcinoma cell line harbouring the same mutation

1995 • 60 citations

rsc: a novel oncogene with structural and functional homology with the gene family of exchange factors for Ral

1997 • 60 citations

Ras interference as cancer therapy

2003 • 53 citations

Ras Signaling Pathway Proteins as Therapeutic Targets

2001 • 51 citations

RalGEF2, a Pleckstrin Homology Domain Containing Guanine Nucleotide Exchange Factor for Ral

2000 • 49 citations

Predictive Factors for Pancreatic Cancer in Patients with Chronic Pancreatitis in Association with K-rasGene Mutation

2004 • 48 citations

Detection of RAS mutations in archival testicular germ cell tumors by polymerase chain reaction and oligonucleotide hybridization

1992 • 44 citations

The dominant negative H-ras mutant, N116Y, suppresses growth of metastatic human pancreatic cancer cells in the liver of nude mice

2000 • 44 citations

A Novel Activating Mutation of the K-ras Gene in Human Primary Colon Adenocarcinoma

2000 • 42 citations

Mutational spectrum of K‐ras oncogene among Indian patients with gallbladder cancer

2004 • 42 citations

Toward antisense oligonucleotide therapy for cancer: ISIS compounds in clinical development.

1999 • 40 citations

Suppression of Pancreatic Cancer by the Dominant NegativerasMutant, N116Y

1996 • 40 citations

A randomized, phase II ECOG trial of two dose levels of temsirolimus (CCI-779) in patients with extensive stage small cell lung cancer in remission after induction chemotherapy. A preliminary report

2005 • 37 citations

Mutated Ras Peptides as Vaccines in Immunotherapy of Cancer

1998 • 37 citations

High frequency of ki‐ras amplification and p53 gene mutations in adenocarcinomas of the human esophagus

1995 • 37 citations

Detection and Clinical Correlations of <i>ras</i> Gene Mutations in Human Ovarian Tumors

1999 • 35 citations

A dominant negative RAS-specific guanine nucleotide exchange factor reverses neoplastic phenotype in K-ras transformed mouse fibroblasts

2000 • 35 citations

Molecular alterations in chronic ulcerative colitis-associated and sporadic hyperplastic polyps: a comparative analysis

2002 • 35 citations

Targeted therapy in advanced colon cancer: the role of new therapies

2004 • 33 citations

Inhibitors of the ras oncogene as therapeutic targets

2002 • 32 citations

Antitumor effect and potentiation or reduction in cytotoxic drug activity in human colon carcinoma cells by the Raf kinase inhibitor (RKI) BAY 43-9006

2003 • 31 citations

NF1 modulates the effects of ras oncogenes: Evidence of other NF1 function besides its GAP activity

2003 • 28 citations

Activated ras genes occur in human actinic keratoses, premalignant precursors to squamous cell carcinomas

1995 • 28 citations

Intraperitoneal injection of adenovirus expressing antisense K-ras RNA suppresses peritoneal dissemination of hamster syngeneic pancreatic cancer without systemic toxicity

2004 • 27 citations

Suppression of Erk activation andin vivo growth in esophageal cancer cells by the dominant negativeRas mutant, N116Y

1998 • 27 citations

Unique K-ras mutational pattern in pancreatic adenocarcinoma from Taiwanese patients

2002 • 26 citations

Blocked Pathways: FTIs Shut Down Oncogene Signals

2003 • 25 citations

Identification of Key Residues in the A-Raf Kinase Important for Phosphoinositide Lipid Binding Specificity

2005 • 25 citations

K-ras oncogene codon 12 point mutations in testicular cancer.

1993 • 22 citations

The kinase domain of MEKK1 induces apoptosis by dysregulation of MAP kinase pathways

2003 • 20 citations

P120-GAP associated with syndecan-2 to function as an active switch signal for Src upon transformation with oncogenic ras

2005 • 20 citations

Suppression of various human tumor cell lines by a dominant negative H-ras mutant.

1994 • 20 citations

Overexpression of c-K-ras, c-N-ras and transforming growth factor β co-segregate with tumorigenicity in morphologically transformed C3H 10T1/2 cell lines

1994 • 20 citations

trans-Dominant suppressor mutations of the H-ras oncogene.

1990 • 19 citations

Molecular assessment of depth of myometrial invasion in stage I endometrial cancer: a model based on K-ras mutation analysis

2003 • 19 citations

Chemistry and biology of ras farnesyltransferase

2002 • 17 citations

Preclinical development of ARRY-142886, a potent and selective MEK inhibitor

2004 • 17 citations

Development of new anti-cancer peptides from conformational energy analysis of the oncogenic ras-p21 protein and its complexes with target proteins

2004 • 16 citations

[32] Ras-Raf complexes: Analyses of complexes formed in Vivo

1995 • 15 citations

Trap RACK1 with Ras to mobilize Src signaling at syndecan-2/p120-GAP upon transformation with oncogenic ras

2005 • 14 citations

Detection of High Incidence of H‐RAS Oncogene Point Mutations in Acute Myelogenous Leukemia

1993 • 14 citations

K‐ras mutations in nonmucinous ovarian epithelial tumors

1998 • 11 citations

Farnesyltransferase inhibitors

2003 • 9 citations

Retroviral gene transfer of dominant negative Raf-1 mutants suppresses Ha-ras-induced transformation and delays tumor formation

2000 • 8 citations

N997B: Phase II trial of CCI-779 in recurrent glioblastoma multiforme (GBM): Updated results and correlative laboratory analysis

2005 • 7 citations

Activated Conformations of theras-gene-Encoded p21 Protein. 1. An Energy-Refined Structure for the Normal p21 Protein Complexed with GDP

1992 • 7 citations

Anti-tumor activity of low-dose single agent CCI-779 for relapsed mantle celllLymphoma: A phase II trial in the North Central Cancer Treatment Group

2005 • 4 citations

K-ras Oncogene Codon 12 Point Mutations in Testicular Cancer

1993 • 4 citations

Activated Conformations of theras-Gene-Encoded p21 Protein. 2. Comparison of the Computed and High-Resolution X-ray Crystallographic Structures of Gly-12 p21

1993 • 3 citations

Deleted Work

1955 • 0 citations