- Inhibition of mutated, activated BRAF in metastatic melanoma
Keith T Flaherty
Abramson Cancer Center of the University of Pennsylvania, Philadelphia, USA
N Engl J Med 363:809-19. 2010
..The identification of somatic mutations in the gene encoding the serine-threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease...
- Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Division of Dermatology Department of Medicine, UCLA s Jonsson Comprehensive Cancer Center, 52 121 CHS, Los Angeles, California 90095 1750, USA
Nature 468:973-7. 2010
- RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Poulikos I Poulikakos
Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Nature 480:387-90. 2011
- Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma
Robert J Motzer
Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
J Clin Oncol 27:3584-90. 2009
..Final survival analyses and updated results are reported...
- COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Cory M Johannessen
Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 468:968-72. 2010
- Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
Nat Chem Biol 1:112-9. 2005
..Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies...
- RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF
Poulikos I Poulikakos
Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Nature 464:427-30. 2010
..In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS...
- Glucosinolate metabolites required for an Arabidopsis innate immune response
Nicole K Clay
Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
Science 323:95-101. 2009
..Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens...
- RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
Genentech, South San Francisco, California 94080, USA
Nature 464:431-5. 2010
..Furthermore, this work provides new insights into the therapeutic use of ATP-competitive RAF inhibitors...
- Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3
Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2170, USA
Nat Immunol 6:777-84. 2005
..These findings demonstrate a regulatory function for GSK3 in modulating the inflammatory response...
- Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling
Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, D1542, Boston, MA, USA
J Clin Oncol 29:3085-96. 2011
..These results provide an instructive framework for assessing mechanisms of acquired resistance to kinase inhibition and illustrate the use of emerging technologies in a manner that may accelerate personalized cancer medicine...
- PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression
Kim H T Paraiso
Department of Molecular Oncology, The Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, Florida, USA
Cancer Res 71:2750-60. 2011
..In conclusion, we have shown for the first time that loss of PTEN contributes to intrinsic BRAF inhibitor resistance via the suppression of BIM-mediated apoptosis...
- Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance
Division of Dermatology, Department of Medicine, University of California, Los Angeles, 52 121 CHS, 10833 Le Conte Avenue, California 90095 1750, USA
Nat Commun 3:724. 2012
..Thus, alternative clinical strategies may potentially overcome distinct modes of extracellular signal-regulated kinase reactivation underlying acquired B-RAF inhibitor resistance in melanoma...
- Bacterial charity work leads to population-wide resistance
Henry H Lee
Howard Hughes Medical Institute, Center for BioDynamics, Boston, Massachusetts 02115, USA
Nature 467:82-5. 2010
- Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor
Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Nat Med 10:55-63. 2004
..These results suggest that the use of GSK-3-specific inhibitors such as BIO may have practical applications in regenerative medicine...
- Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
Plexxikon, Inc, 91 Bolivar Drive, Berkeley, CA 94710, USA
Proc Natl Acad Sci U S A 105:3041-6. 2008
- Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study
Daniel Y C Heng
FRCPC, Department of Medical Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada
J Clin Oncol 27:5794-9. 2009
..There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy...
- EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib
Ryan B Corcoran
Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA
Cancer Discov 2:227-35. 2012
..These findings support evaluation of combined RAF and EGFR inhibition in BRAF mutant CRC patients...
- RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors
Patrick A Oberholzer
Broad Institute of Massachusetts Institute of Technology, Cambridge, USA
J Clin Oncol 30:316-21. 2012
..The potential of these agents to promote secondary malignancies is concerning. We analyzed cSCC and KA lesions for genetic mutations in an attempt to identify an underlying mechanism for their formation...
- Sunitinib versus interferon alfa in metastatic renal-cell carcinoma
Robert J Motzer
Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
N Engl J Med 356:115-24. 2007
..Since sunitinib malate has shown activity in two uncontrolled studies in patients with metastatic renal-cell carcinoma, a comparison of the drug with interferon alfa in a phase 3 trial is warranted...
- Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription
M P Coghlan
Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Essex, UK
Chem Biol 7:793-803. 2000
..This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3...
- The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner
Eric W Joseph
Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA
Proc Natl Acad Sci U S A 107:14903-8. 2010
..This selectivity may lead to a broader therapeutic index and help explain the greater antitumor activity observed with this drug than with MEK inhibitors...
- Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer
Patrick C Ma
Section of Hematology Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, Chicago, Illinois, USA
Cancer Res 65:1479-88. 2005
..These results indicate that c-Met inhibition will be an important therapeutic strategy against NSCLC to improve its clinical outcome...
- Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines
Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Gottingen, D 37073 Gottingen, Germany
J Pineal Res 47:109-26. 2009
..AMK easily interacts with aromates, forms adducts with tyrosyl and tryptophanyl residues, and may modify proteins...
- Clinical studies of histone deacetylase inhibitors
H Miles Prince
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Australia and University of Melbourne, Parkville, Victoria, Australia
Clin Cancer Res 15:3958-69. 2009
..The use of the biomarker of histone hyperacetylation has been useful as a guide to target specificity, but generally does not predict for response and the search for more clinically relevant biomarkers must continue...
- KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel
H S Wang
Institute of Molecular Cardiology, Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
Science 282:1890-3. 1998
..The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current...
- The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms
Kim H T Paraiso
The Department of Molecular Oncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
Clin Cancer Res 18:2502-14. 2012
..The clinical use of BRAF inhibitors is being hampered by the acquisition of drug resistance. This study shows the potential therapeutic use of the HSP90 inhibitor (XL888) in six different models of vemurafenib resistance...
- Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study
Andrew X Zhu
Division of Hematology Oncology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA
J Clin Oncol 27:3027-35. 2009
..To assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response...
- Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
Plexxikon Inc, 91 Bolivar Drive, Berkeley, California 94710, USA
Nature 467:596-9. 2010
..These data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase activity...
- Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma
Laboratory of Cancer Genetics, Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
Cancer Res 70:1063-71. 2010
..Our results reveal IL-8 as an important contributor to sunitinib resistance in ccRCC and a candidate therapeutic target to reverse acquired or intrinsic resistance to sunitinib in this malignancy...
- In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship
Dirk B Mendel
Preclinical Research and Exploratory Development, SUGEN, Inc, South San Francisco, California 94080, USA
Clin Cancer Res 9:327-37. 2003
..The pharmacokinetic/pharmacodynamic relationship established for SU11248 in these preclinical studies has aided in the design, selection, and evaluation of dosing regimens being tested in human trials...
- Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways
Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA
Circ Res 88:888-94. 2001
..These data support a role for nox1 in redox signaling in VSMCs and provide insight into the molecular identity of the VSMC NAD(P)H oxidase and its potentially critical role in vascular disease...
- Combinatorial treatments that overcome PDGFRβ-driven resistance of melanoma cells to V600EB-RAF inhibition
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Cancer Res 71:5067-74. 2011
..Together, our findings offer a rational strategy to guide clinical testing in preidentified subsets of patients who relapse during treatment with (V600E)B-RAF inhibitors...
- SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types
T A Fong
SUGEN, Inc, South San Francisco, California 94080, USA
Cancer Res 59:99-106. 1999
..These findings support that pharmacological inhibition of the enzymatic activity of the vascular endothelial growth factor receptor represents a novel strategy for limiting the growth of a wide variety of tumor types...
- Activation of MAPK kinase 9 induces ethylene and camalexin biosynthesis and enhances sensitivity to salt stress in Arabidopsis
State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100094, China
J Biol Chem 283:26996-7006. 2008
..The results reported here reveal that the MKK9-MPK3/MPK6 cascade participates in the regulation of the biosynthesis of ethylene and camalexin and may be an important axis in the stress responses of Arabidopsis...
- Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial
George D Demetri
Ludwig Center at Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
Lancet 368:1329-38. 2006
- Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
Jill C Rubinstein
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA
J Transl Med 8:67. 2010
..Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations...
- Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma
Brian I Rini
Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue, Desk R35, Cleveland, OH 44195, USA
J Clin Oncol 26:3743-8. 2008
..To assess the safety and efficacy of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma (mRCC) and explore biomarkers for sunitinib response...
- Sunitinib: from rational design to clinical efficacy
Laura Q M Chow
Department of Medical Oncology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
J Clin Oncol 25:884-96. 2007
- Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations
James G Greger
Oncology R and D Translational Research, GlaxoSmithKline, Collegeville, Pennsylvania, USA
Mol Cancer Ther 11:909-20. 2012
..In addition, these resistant clones respond to the combination of GSK2126458 with GSK2118436 or GSK1120212. Clinical trials are ongoing or planned to test these combinations...
- Analytical performance of a real-time PCR-based assay for V600 mutations in the BRAF gene, used as the companion diagnostic test for the novel BRAF inhibitor vemurafenib in metastatic melanoma
Roche Molecular Diagnostics, Pleasanton, CA 94588, USA
Diagn Mol Pathol 21:1-8. 2012
..A simple 1:2 dilution resulted in a valid test result of 76% in such cases. The cobas test is a reproducible assay that detects some non-V600E mutations and is more accurate than direct sequencing in detecting BRAFV600E...
- Single-dose intravenous toxicity study of IRDye 800CW in Sprague-Dawley rats
Milton V Marshall
Baylor College of Medicine, Houston, TX, USA
Mol Imaging Biol 12:583-94. 2010
..Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate...
- Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium
D Z Chen
North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030, USA
J Nutr 131:3294-302. 2001
- RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models
Discovery Oncology, Hoffmann La Roche, Inc, Nutley, New Jersey, USA
Cancer Res 70:5518-27. 2010
..There was no toxicity observed in any dose group in any of the in vivo models tested. Our findings offer evidence of the potent antitumor activity of RG7204 against melanomas harboring the mutant BRAF(V600E) gene...
- An overview of small-molecule inhibitors of VEGFR signaling
S Percy Ivy
Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA
Nat Rev Clin Oncol 6:569-79. 2009
..The on-target effects seem to be mechanistically based and predicted by VEGFR inhibition. Small-molecule inhibitors of angiogenesis are active in a wide variety of malignancies and fill a unique niche for cancer therapeutics...
- Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathway
Department of Medicine, Division of Hematology Oncology, University of California Los Angeles, Los Angeles, California, United States of America
PLoS ONE 6:e28973. 2011
..Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway...
- Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study
Hospital Universitario Fundacion Alcorcon, Alcorcon, Spain
Lancet Oncol 12:1143-50. 2011
..Because there are no validated molecular predictors of response or toxicity to sunitinib, we aimed to identify genetic markers predictive of outcome and toxic effects...
- Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752
Gromoslaw A Smolen
Cancer Center and Department of Pathology, Molecular Pathology Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 103:2316-21. 2006
..MET amplification may thus identify a subset of epithelial cancers that are uniquely sensitive to disruption of this pathway and define a patient group that is appropriate for clinical trials of targeted therapy using MET inhibitors...
- Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib
Brian I Rini
Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA
J Natl Cancer Inst 103:763-73. 2011
..We evaluated the association of sunitinib-induced HTN with antitumor efficacy and HTN-associated adverse events in patients with metastatic renal cell carcinoma...
- Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases
Laboratory of Pharmacognosy and Laboratory of Pharmaceutical Chemistry, Department of Pharmacy, University of Athens, Panepistimiopolis Zografou, GR 15771 Athens, Greece
J Med Chem 47:935-46. 2004
..Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3...
- Indole as an intercellular signal in microbial communities
Jin Hyung Lee
School of Display and Chemical Engineering, Yeungnam University, Gyeongsan, Korea
FEMS Microbiol Rev 34:426-44. 2010
..It appears indole plays an important role in bacterial physiology, ecological balance, and possibly human health. Here we discuss our current knowledge and perspectives on indole signaling...
- Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases
Division of Epigenetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Cancer Res 65:6305-11. 2005
..These results establish RG108 as a DNA methyltransferase inhibitor with fundamentally novel characteristics that will be particularly useful for the experimental modulation of epigenetic gene regulation...
- MEK-independent survival of B-RAFV600E melanoma cells selected for resistance to apoptosis induced by the RAF inhibitor PLX4720
Chen Chen Jiang
Immunology and Oncology Unit, Newcastle, New South Wales, Australia
Clin Cancer Res 17:721-30. 2011
..To examine mechanisms that determine long-term responses of B-RAF(V600E) melanoma cells to B-RAF inhibitors...
- Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor
Michael C Heinrich
Division of Hematology Oncology, Department of Medicine and Cell and Developmental Biology, Portland Veterans Affairs Medical Center and Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
J Clin Oncol 26:5352-9. 2008
..We evaluated the impact of primary and secondary kinase genotype on sunitinib activity...
- The Arabidopsis YUCCA1 flavin monooxygenase functions in the indole-3-pyruvic acid branch of auxin biosynthesis
Anna N Stepanova
Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA
Plant Cell 23:3961-73. 2011
- Motesanib diphosphate in progressive differentiated thyroid cancer
Steven I Sherman
Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M D Anderson Cancer Center, Houston 77230 1402, USA
N Engl J Med 359:31-42. 2008
..Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT...
- Molecular pathobiology of gastrointestinal stromal sarcomas
Christopher L Corless
Department of Pathology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
Annu Rev Pathol 3:557-86. 2008
- BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy
Boehringer Ingelheim Austria GmbH, Vienna, Austria and Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany
Cancer Res 68:4774-82. 2008
..These distinctive pharmacokinetic and pharmacodynamic properties may help explain clinical observations with BIBF 1120, currently entering phase III clinical development...
- Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer
Mark A Socinski
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
J Thorac Oncol 5:354-60. 2010
- Mechanisms of resistance to RAF inhibitors in melanoma
Andrew E Aplin
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
J Invest Dermatol 131:1817-20. 2011
..Bi-directional translational efforts are now essential to determine the mechanisms underlying acquired/secondary and intrinsic resistance to RAF inhibitors...
- PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells
Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA
Pigment Cell Melanoma Res 23:190-200. 2010
..The results suggest that the drug can confer an advantage to BRAF(WT) primary and metastatic tumor cells in vivo and provide markers for monitoring clinical responses...
- Phase II study of sunitinib as first-line treatment of urothelial cancer patients ineligible to receive cisplatin-based chemotherapy: baseline interleukin-8 and tumor contrast enhancement as potential predictive factors of activity
Medical Oncology Service, University Hospital del Mar, Barcelona, Spain
Ann Oncol 22:2646-53. 2011
..This trial was designed to assess the activity of sunitinib as first-line treatment in patients with metastatic urothelial cancer ineligible for cisplatin and to explore molecular and imaging variables predictive of clinical benefit...
- Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer
Carlos H Barrios
PUCRS School of Medicine, Centro de Pesquisa em Oncologia, Jardim Botanico, Porto Alegre, RS, 90610 000, Brazil
Breast Cancer Res Treat 121:121-31. 2010
..51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC...
- Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma
Jose A Karam
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Eur Urol 59:619-28. 2011
..Animal models are instrumental in understanding disease pathophysiology and mechanisms of therapy action and resistance in vivo...
- Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells
Divisions of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California, USA
Cancer Res 69:2506-13. 2009
..These results suggest that Stat3 activity is important for RCC response to sunitinib, and Stat3 inhibition permits the direct proapoptotic activity of sunitinib on tumor cells and positive effects on tumor immunologic microenvironment...
- Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure
Center for Sarcoma and Bone Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Eur J Cancer 45:1959-68. 2009
- The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies
Departments of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York, USA
Cancer Res 69:2514-22. 2009
..These data suggest that sunitinib can be used to reverse immune suppression and as a potentially useful adjunct for enhancing the efficacy of immune-based cancer therapy for advanced malignancies...
- Akt3-mediated resistance to apoptosis in B-RAF-targeted melanoma cells
Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Cancer Res 70:6670-81. 2010
..These findings delineate how mutant B-RAF protects melanoma cells from apoptosis and provide insight into possible resistance mechanisms to B-RAF inhibitors...
- Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer
Martin J Schlumberger
Institut Gustave Roussy, rue Camille Desmoulins, 94805 Villejuif Cedex, France
J Clin Oncol 27:3794-801. 2009
- Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained
Jennifer S Ko
Department of Immunology, Taussig Cancer Institute, and Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio, USA
Cancer Res 70:3526-36. 2010
- Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors
Lee S Rosen
Premiere Oncology, Santa Monica, CA, USA
J Clin Oncol 25:2369-76. 2007
..This phase I, dose-finding study evaluated the safety, pharmacokinetics, and pharmacodynamics of AMG 706 in patients with refractory advanced solid tumors...
- Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1
Andrew D Napper
Elixir Pharmaceuticals, One Kendall Square, Cambridge, Massachusetts 02139, USA
J Med Chem 48:8045-54. 2005
High-throughput screening against the human sirtuin SIRT1 led to the discovery of a series of indoles as potent inhibitors that are selective for SIRT1 over other deacetylases and NAD-processing enzymes...
- The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint
Research Institute of Molecular Pathology, Dr Bohr Gasse 7, 1030 Vienna, Austria
J Cell Biol 161:281-94. 2003
..Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling...
- c-Met is a potentially new therapeutic target for treatment of human melanoma
Departments of Hematology Oncology and Pathology, University of Chicago Medical Center, Chicago, Illinois 60607, USA
Clin Cancer Res 13:2246-53. 2007
..In this study, we investigated the role of c-Met in melanoma biology using a novel small-molecule tyrosine kinase inhibitor SU11274 and small interfering (si) RNA against the receptor...
- Inhibition of angiogenesis and invasion by 3,3'-diindolylmethane is mediated by the nuclear factor-kappaB downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA
Cancer Res 67:3310-9. 2007
- Sequential FDG-PET/CT as a biomarker of response to Sunitinib in metastatic clear cell renal cancer
Department of Nuclear Medicine, University College Hospital, London, UK
Clin Cancer Res 17:6021-8. 2011
..Three sequential scans were conducted to determine whether the timing of the investigation was relevant...
- Why plants need more than one type of auxin
Institute of Experimental Botany, ASCR, Rozvojova 263, 16502 Praha 6, Czech Republic
Plant Sci 180:454-60. 2011
..We present a scheme for homeostatic regulation of IAA levels that embraces other endogenous auxins in terms of the described mechanism of auxin action including its receptor and downstream signal transduction events...
- GSK-3-selective inhibitors derived from Tyrian purple indirubins
CNRS, Cell Cycle Group, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
Chem Biol 10:1255-66. 2003
..BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6-bromoindirubins thus provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3...
- Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms
Department of Neurosurgery, Medical Faculty of the University of Heidelberg, Mannheim, Germany
FASEB J 18:338-40. 2004
- Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice
School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Universiteitssingel 50, NL 6229 ER Maastricht, The Netherlands
Prog Neuropsychopharmacol Biol Psychiatry 35:510-22. 2011
..Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice...
- Myzus persicae (green peach aphid) feeding on Arabidopsis induces the formation of a deterrent indole glucosinolate
Jae Hak Kim
Boyce Thompson Institute for Plant Research, Tower Road, Ithaca, NY 14853, USA
Plant J 49:1008-19. 2007
..Together, these results demonstrate that, in response to aphid feeding, Arabidopsis plants convert one indole glucosinolate to another that provides a greater defensive benefit...
- Molecular mechanisms of indirubin and its derivatives: novel anticancer molecules with their origin in traditional Chinese phytomedicine
Division of Food Chemistry and Environmental Toxicology, Department of Chemistry, University of Kaiserslautern, P O Box 3049, 67663, Kaiserslautern, Germany
J Cancer Res Clin Oncol 130:627-35. 2004
..This novel family of compounds holds strong promise for clinical anticancer activity and might be useful also in several important noncancer indications, including Alzheimer's disease or diabetes...
- Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects
Gregory A Reed
Departments of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
Cancer Epidemiol Biomarkers Prev 17:2619-24. 2008
..We conclude that BR-DIM is well tolerated at single doses of up to 200 mg, and that increasing the dose to 300 mg did not result in an increase in C(max)...
- Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells
Hyun Ju Choi
Department of Food Science and Nutrition, Hallym University, Chuncheon, Republic of Korea
BMC Gastroenterol 9:39. 2009
..In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells...
- Identification of indole glucosinolate breakdown products with antifeedant effects on Myzus persicae (green peach aphid)
Jae Hak Kim
Boyce Thompson Institute for Plant Research, Ithaca, NY 14853, USA
Plant J 54:1015-26. 2008
..persicae. Therefore, the post-ingestive breakdown of indole glucosinolates provides a defense against herbivores such as aphids that can avoid glucosinolate activation by plant myrosinases...
- Down-regulation of uPA and uPAR by 3,3'-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells
Department of Pathology, Barbara Ann Karmanos Cancer Center, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
J Cell Biochem 108:916-25. 2009
- The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)
Oncological Endocrinology, AOU San Giovanni Battista, University of Turin, Turin, Italy
Breast Cancer Res Treat 124:667-75. 2010
..In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease...
- Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors
Chandrajit P Raut
Department of Surgery, Brigham and Women s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
J Clin Oncol 24:2325-31. 2006
..To assess the role of surgery in multimodality management of GISTs, we studied postoperative outcomes in patients treated with targeted kinase inhibitors for advanced GIST...
- SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models
Aaron J Schueneman
Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
Cancer Res 63:4009-16. 2003
..Moreover, inhibition of angiogenesis well beyond radiation therapy may be a promising treatment paradigm for refractory human neoplasms...
- Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors
Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
J Biol Chem 280:26729-34. 2005
..Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors...
- Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges
Novartis Institutes for BioMedical Research, Cambridge, MA, USA
Cancer Lett 280:233-41. 2009
- Gene expression profiling revealed survivin as a target of 3,3'-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells
Km Wahidur Rahman
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
Cancer Res 66:4952-60. 2006
..These results suggest that targeting survivin by 3,3'-diindolylmethane could be a new and novel approach for the prevention and/or treatment of breast cancer...
- Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032
Jonas N Søndergaard
Department of Medicine, Division of Hematology Oncology, University of California Los Angeles, Los Angeles, CA, USA
J Transl Med 8:39. 2010
..In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity...
- The ABC transporter BcatrB from Botrytis cinerea exports camalexin and is a virulence factor on Arabidopsis thaliana
Francesca L Stefanato
Department of Biology, University of Fribourg, Chemin du Musée 8, CH 1700 Fribourg, Switzerland
Plant J 58:499-510. 2009
..Here we demonstrate that an ABC transporter is a virulence factor that increases tolerance of the pathogen towards a phytoalexin, and the complete restoration of virulence on host plants lacking this phytoalexin...
- Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction
Department of Internal Medicine, Comprehensive Cancer Center, Life Sciences Institute, University of Michigan, 1500 E Medical Center Drive, Ann Arbor, 48109, USA
J Med Chem 49:3432-5. 2006
..MI-63 has excellent specificity over cancer cells with deleted p53 and shows a minimal toxicity to normal cells...
- AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts
Department of Oncology Research, Amgen, Inc, Thousand Oaks, CA 91320 1799, USA
Cancer Res 66:8715-21. 2006
..In summary, AMG 706 is an orally bioavailable, well-tolerated multikinase inhibitor that is presently under clinical investigation for the treatment of human malignancies...
- The specificities of protein kinase inhibitors: an update
Division of Signal Transduction Therapy, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
Biochem J 371:199-204. 2003
..33 microM) and p38-regulated/activated kinase (PRAK; IC(50)=1.0 microM)...
- First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study
Karolinska Institutet and University Hospital, 171 76 Stockholm, Sweden
J Clin Oncol 30:921-9. 2012
..To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer (ABC) versus docetaxel alone...
- Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli
Department of Biological Sciences, Stanford University, California 94305 5020
J Bacteriol 173:6009-17. 1991
..Our studies assign roles to the three permeases in tryptophan transport under different physiological conditions...
- Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial
Nicholas J Robert
Virginia Cancer Specialists, US Oncology, Fairfax, VA, USA
Clin Breast Cancer 11:82-92. 2011
- Antioxidant activity of 5,10-dihydroindeno[1,2-b]indoles containing substituents on dihydroindeno part
Department of Chemistry, Faculty of Sciences, Ataturk University, 25240 Erzurum, Turkey
Bioorg Med Chem 17:6583-9. 2009
An efficient synthesis of 5,10-dihydroindeno[1,2-b]indoles (3a-t) containing substituents such as methoxy, hydroxyl, and halogen (F, Cl, and Br) on indeno part was described...