Issues and progress with protein kinase inhibitors for cancer treatment

Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2

2001 • 11,070 citations

Mutations of the BRAF gene in human cancer

2002 • 10,249 citations

Gene expression profiling predicts clinical outcome of breast cancer

2002 • 9,314 citations

The Protein Kinase Complement of the Human Genome

2002 • 7,708 citations

Untangling the ErbB signalling network

2001 • 6,623 citations

The phosphatidylinositol 3-Kinase–AKT pathway in human cancer

2002 • 5,914 citations

The Phosphoinositide 3-Kinase Pathway

2002 • 5,427 citations

Oncogenic kinase signalling

2001 • 3,632 citations

Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome

2001 • 2,749 citations

Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses

2001 • 2,560 citations

Gene expression correlates of clinical prostate cancer behavior

2002 • 2,504 citations

Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning

2002 • 2,400 citations

Effect of the Tyrosine Kinase Inhibitor STI571 in a Patient with a Metastatic Gastrointestinal Stromal Tumor

2001 • 2,038 citations

TOR, a Central Controller of Cell Growth

2000 • 1,919 citations

Clinical translation of angiogenesis inhibitors

2002 • 1,518 citations

Protein kinase Cα activates RAF-1 by direct phosphorylation

1993 • 1,282 citations

FAK integrates growth-factor and integrin signals to promote cell migration

2000 • 1,215 citations

Phase I and Pharmacologic Study of OSI-774, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced Solid Malignancies

2001 • 995 citations

A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor.

2001 • 988 citations

Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR

2001 • 981 citations

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

1999 • 970 citations

Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor.

2000 • 934 citations

Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571).

2002 • 925 citations

Insulin-Like Growth Factor-I Receptor Signaling and Resistance to Trastuzumab (Herceptin)

2001 • 868 citations

Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells

1995 • 859 citations

Phase I Safety, Pharmacokinetic, and Pharmacodynamic Trial of ZD1839, a Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Five Selected Solid Tumor Types

2002 • 828 citations

Fluorescence molecular tomography resolves protease activity in vivo

2002 • 814 citations

Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase.

2000 • 766 citations

Phase I Studies of Anti–Epidermal Growth Factor Receptor Chimeric Antibody C225 Alone and in Combination With Cisplatin

2000 • 748 citations

Scatter-factor and semaphorin receptors: cell signalling for invasive growth

2002 • 734 citations

Hsp90 inhibitors as novel cancer chemotherapeutic agents

2002 • 673 citations

Linkage of G Protein-Coupled Receptors to the MAPK Signaling Pathway Through PI 3-Kinase γ

1997 • 671 citations

Phase II Trial of ZD1839 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

2003 • 616 citations

Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 Is Generally Well-Tolerated and Has Activity in Non–Small-Cell Lung Cancer and Other Solid Tumors: Results of a Phase I Trial

2002 • 583 citations

An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity inPten^+/−mice

2001 • 574 citations

Management of malignant gastrointestinal stromal tumours

2002 • 574 citations

Modulation of radiation response after epidermal growth factor receptor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics, and tumor angiogenesis.

2000 • 549 citations

Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling.

2002 • 508 citations

In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody.

2000 • 498 citations

Pharmacodynamic Studies of the Epidermal Growth Factor Receptor Inhibitor ZD1839 in Skin From Cancer Patients: Histopathologic and Molecular Consequences of Receptor Inhibition

2002 • 490 citations

Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis

2001 • 471 citations

Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy

2001 • 452 citations

Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts.

1993 • 430 citations

mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer.

2001 • 421 citations

Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: dynamics of receptor inhibition in situ and antitumor effects in athymic mice.

1999 • 419 citations

Targeting the epidermal growth factor receptor for cancer therapy.

2002 • 412 citations

Molecular Targeting of Platelet-Derived Growth Factor B by Imatinib Mesylate in a Patient With Metastatic Dermatofibrosarcoma Protuberans

2002 • 373 citations

The TOR Kinases Link Nutrient Sensing to Cell Growth

2001 • 348 citations

Activity of rapamycin (AY-22,989) against transplanted tumors.

1984 • 337 citations

Development of anticancer drugs targeting the MAP kinase pathway

2000 • 322 citations

A p34cdc2 survival checkpoint in cancer

2002 • 317 citations

Ras and Rho regulation of the cell cycle and oncogenesis

2001 • 316 citations

Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells.

1999 • 313 citations

Progress in understanding the molecular pathogenesis of human lung cancer

1998 • 291 citations

BAY 43-9006: Preclinical Data

2002 • 289 citations

Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth

2002 • 276 citations

Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy.

2001 • 263 citations

Molecular mechanisms for the control of translation by insulin

1997 • 257 citations

Cell cycle targets of Ras/Raf signalling

1998 • 257 citations

Dose-Finding and Pharmacokinetic Study of Cisplatin, Gemcitabine, and SU5416 in Patients With Solid Tumors

2002 • 253 citations

Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis.

2003 • 253 citations

Pharmacodynamic Studies of the Epidermal Growth Factor Receptor Inhibitor ZD1839 in Skin From Cancer Patients: Histopathologic and Molecular Consequences of Receptor Inhibition

2002 • 244 citations

Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro.

1995 • 230 citations

Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition.

2001 • 229 citations

Mechanisms and Future Directions for Angiogenesis-Based Cancer Therapies

2002 • 228 citations

The immunosuppressive macrolide RAD inhibits growth of human Epstein–Barr virus-transformed B lymphocytes in vitro and in vivo : A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders

2000 • 215 citations

Regulation of cell growth and cyclin D1 expression by the constitutively active FRAP-p70s6K pathway in human pancreatic cancer cells.

1999 • 211 citations

c-Jun NH2-terminal Kinase-mediated Activation of Interleukin-1β Converting Enzyme/CED-3-like Protease during Anticancer Drug-induced Apoptosis

1997 • 207 citations

New antitumor substances of natural origin

1981 • 197 citations

A Proline-Rich Sequence Unique to MEK1 and MEK2 Is Required for Raf Binding and Regulates MEK Function

1995 • 196 citations

A phase II trial of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor OSI-774, following platinum-based chemotherapy, in patients (pts) with advanced-EGFR-expressing, non-small cell lung cancer (NSCLC)

2001 • 194 citations

PI3-kinase inhibition: a target for drug development?

2000 • 194 citations

Targeting the epidermal growth factor receptor

2004 • 183 citations

Final results from a phase II trial of ZD1839 ("Iressa") for patients with advanced non-small-cell lung cancer (IDEAL 1)

2002 • 175 citations

Studies on the Mechanism of Resistance to Rapamycin in Human Cancer Cells

1998 • 173 citations

p38 and Chk1 kinases: different conductors for the G2/M checkpoint symphony

2002 • 172 citations

Rapamycin inhibits constitutive p70s6k phosphorylation, cell proliferation, and colony formation in small cell lung cancer cells.

1996 • 170 citations

The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-met-urokinase plasminogen activator-plasmin proteolytic network.

2000 • 167 citations

Influence of Unrecognized Molecular Heterogeneity on Randomized Clinical Trials

2002 • 165 citations

Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells.

2001 • 162 citations

New Insights into the Interaction of Ras with the Plasma Membrane

1999 • 154 citations

RAPAMYCIN, A POTENT IMMUNOSUPPRESSIVE DRUG, CAUSES PROGRAMMED CELL DEATH IN B LYMPHOMA CELLS

1995 • 148 citations

p53/p21(CIP1) cooperate in enforcing rapamycin-induced G(1) arrest and determine the cellular response to rapamycin.

2001 • 137 citations

Phase I Clinical/Pharmacokinetic and Pharmacodynamic Trial of the c-raf-1 Antisense Oligonucleotide ISIS 5132 (CGP 69846A)

1999 • 131 citations

Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment.

2001 • 130 citations

A phase I trial of c-Raf kinase antisense oligonucleotide ISIS 5132 administered as a continuous intravenous infusion in patients with advanced cancer.

2000 • 128 citations

Dose-Finding and Pharmacokinetic Study of Cisplatin, Gemcitabine, and SU5416 in Patients With Solid Tumors

2002 • 126 citations

Novel Small Molecule Cyclin-Dependent Kinases Modulators in Human Clinical Trials

2003 • 123 citations

Therapeutic potential of ABX-EGF: A fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment

2002 • 123 citations

Inhibition of the Bcr-Abl tyrosine kinase as a therapeutic strategy for CML

2002 • 119 citations

A randomized phase II and pharmacokinetic study of the antisense oligonucleotides ISIS 3521 and ISIS 5132 in patients with hormone-refractory prostate cancer.

2002 • 118 citations

A signal transduction pathway for activation of the mdr1 promoter involves the proto-oncogene c-raf kinase

1993 • 107 citations

Potentiation of apoptosis by flavopiridol in mitomycin-C-treated gastric and breast cancer cells.

1997 • 107 citations

Results of phase I pharmacokinetic and pharmacodynamic studies of the Raf kinase inhibitor BAY 43-9006 in patients with solid tumors

2002 • 106 citations

Phase II randomized study of ISIS 3521 and ISIS 5132 in patients with locally advanced or metastatic colorectal cancer: a National Cancer Institute of Canada clinical trials group study.

2002 • 96 citations

Activation of human raf transforming genes by deletion of normal amino-terminal coding sequences.

1987 • 95 citations

Therapies directed at vascular endothelial growth factor

2002 • 91 citations

Differential sensitivity of cancer cells to inhibitors of the epidermal growth factor receptor family

2002 • 86 citations

Phase II trial with ISIS 5132 in patients with small-cell (SCLC) and non-small cell (NSCLC) lung cancer. A European Organization for Research and Treatment of Cancer (EORTC) Early Clinical Studies Group report

2001 • 82 citations

c-raf-1 depletion and tumor responses in patients treated with the c-raf-1 antisense oligodeoxynucleotide ISIS 5132 (CGP 69846A).

1999 • 77 citations

[29] Inhibition of protein-tyrosine kinases by tyrphostins

1991 • 76 citations

UCN-01 Enhances the In Vitro Toxicity of Clinical Agents in Human Tumor Cell Lines

2000 • 74 citations

Drug inhibition of angiogenesis

2002 • 72 citations

Association of c-Raf expression with survival and its targeting with antisense oligonucleotides in ovarian cancer

2001 • 71 citations

Abrogation of c-Raf expression induces apoptosis in tumor cells

1998 • 69 citations

The cyclin-dependent kinase inhibitor flavopiridol disrupts sodium butyrate-induced p21WAF1/CIP1 expression and maturation while reciprocally potentiating apoptosis in human leukemia cells.

2002 • 68 citations

Molecular diagnosis of lymphoid malignancies by gene expression profiling

2002 • 68 citations

Antitumor activity of a C-raf antisense oligonucleotide in combination with standard chemotherapeutic agents against various human tumors transplanted subcutaneously into nude mice.

1997 • 53 citations

Rate-limiting effects of Cyclin D1 in transformation by ErbB2 predicts synergy between herceptin and flavopiridol.

2002 • 48 citations

Tumor necrosis factor alpha sensitizes low epidermal growth factor receptor (EGFR)-expressing carcinomas for anti-EGFR therapy.

2001 • 46 citations

Species- and gender-related differences in cyclosporine/prednisolone/sirolimus interactions in whole blood lymphocyte proliferation assays.

1998 • 45 citations

Inhibitors of MEK1/2 Interact with UCN-01 to Induce Apoptosis and Reduce Colony Formation in Mammary and Prostate Carcinoma Cells

2002 • 45 citations

Modulation of drug-induced apoptosis by interruption of the protein kinase C signal transduction pathway: a new therapeutic strategy.

1996 • 45 citations

Possible mechanisms of diarrheal side effects associated with the use of a novel chemotherapeutic agent, flavopiridol.

2001 • 44 citations

The Ras-Raf relationship: an unfinished puzzle

2001 • 41 citations

Cell Biology of Lymphatic Metastasis The Potential Role of c-erbB Oncogene Signalling

2000 • 40 citations

Emerging Technologies for HER2 Testing

2002 • 37 citations

GENDER-RELATED ASSESSMENT OF CYCLOSPORINE/PREDNISOLONE/SIROLIMUS INTERACTIONS IN THREE HUMAN LYMPHOCYTE PROLIFERATION ASSAYS1

1998 • 31 citations

Cell Cycle Progression and Proliferation Despite 4BP-1 Dephosphorylation

1999 • 30 citations

P70 S6 kinase assay: a pharmacodynamic monitoring strategy for rapamycin; assay development.

1996 • 25 citations

Bryostatin 1 and UCN-01 Potentiate 1-β-d-Arabinofuranosylcytosine-Induced Apoptosis in Human Myeloid Leukemia Cells through Disparate Mechanisms

2003 • 25 citations

Surprise phase III failure for ZD1839

2002 • 22 citations

Protein kinase C-dependent activation of the tumor necrosis factor receptor-mediated extrinsic cell death pathway underlies enhanced apoptosis in human myeloid leukemia cells exposed to bryostatin 1 and flavopiridol.

2003 • 21 citations

Role of GTPases and GTPase regulatory proteins in oncogenesis.

1993 • 21 citations

First‐And Second‐Generation Antisense Oligonucleotide Inhibitors Targeted Against Human C‐ raf Kinase

2007 • 16 citations

Bay-43-9006

2002 • 10 citations

Altered efficacy and selectivity of tyrosine kinase inhibitors of the activated states of protein tyrosine kinases.

1998 • 9 citations

Pharmacokinetics of single and multiple oral doses of zd 1839 (‘Iressa’), a specific epidermal growth factor receptor tyrosine kinase inhibitor (egfr-tki), in healthy male volunteers

2001 • 7 citations

Regulation by ceramide of epidermal growth factor signal transduction and mitogenesis in cell lines overexpressing the growth factor receptor.

2000 • 6 citations

The Selectivity of Small Molecules Towards Protein Tyrosine Kinases

2001 • 2 citations

Deleted Work

1955 • 0 citations