Brian Druker

Summary

Affiliation: Oregon Health and Science University
Country: USA

Publications

  1. ncbi request reprint STI571 (Gleevec) as a paradigm for cancer therapy
    Brian J Druker
    Leukemia Center, Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA
    Trends Mol Med 8:S14-8. 2002
  2. ncbi request reprint Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
    Brian J Druker
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    N Engl J Med 355:2408-17. 2006
  3. ncbi request reprint Perspectives on the development of a molecularly targeted agent
    Brian J Druker
    Leukemia Center, Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Road, Portland 97201, USA
    Cancer Cell 1:31-6. 2002
  4. ncbi request reprint Imatinib: paradigm or anomaly?
    Brian J Druker
    Howard Hughes Medical Institute
    Cell Cycle 3:833-5. 2004
  5. ncbi request reprint The role of the tyrosine kinase inhibitor STI571 in the treatment of cancer
    M E O'Dwyer
    Leukemia Program, Oregon Health Sciences University L592, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA
    Curr Cancer Drug Targets 1:49-57. 2001
  6. ncbi request reprint David A. Karnofsky Award lecture. Imatinib as a paradigm of targeted therapies
    Brian J Druker
    Howard Hughe Medical Institute and Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    J Clin Oncol 21:239s-245s. 2003
  7. ncbi request reprint 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
    B J Druker
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    N Engl J Med 344:1038-42. 2001
  8. ncbi request reprint Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia
    B J Druker
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    N Engl J Med 344:1031-7. 2001
  9. ncbi request reprint Inhibition of the Bcr-Abl tyrosine kinase as a therapeutic strategy for CML
    Brian J Druker
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, Oregon, OR 97239, USA
    Oncogene 21:8541-6. 2002
  10. ncbi request reprint Imatinib mesylate in the treatment of chronic myeloid leukaemia
    Brian J Druker
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Expert Opin Pharmacother 4:963-71. 2003

Research Grants

  1. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 2004
  2. Cancer and Kinases
    Brian Druker; Fiscal Year: 2005
  3. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 2007
  4. OHSU Cancer Institute
    Brian Druker; Fiscal Year: 2007
  5. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 2009
  6. CBL FUNCTION IN CELLULAR SIGNALING AND TRANSFORMATION
    Brian Druker; Fiscal Year: 2003
  7. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 1999

Detail Information

Publications87

  1. ncbi request reprint STI571 (Gleevec) as a paradigm for cancer therapy
    Brian J Druker
    Leukemia Center, Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA
    Trends Mol Med 8:S14-8. 2002
    ..Finally, the potential use of STI571 with different tumors and the translation of this paradigm to other malignancies are explored...
  2. ncbi request reprint Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
    Brian J Druker
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    N Engl J Med 355:2408-17. 2006
    ..Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy...
  3. ncbi request reprint Perspectives on the development of a molecularly targeted agent
    Brian J Druker
    Leukemia Center, Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Road, Portland 97201, USA
    Cancer Cell 1:31-6. 2002
    ..Lastly, the potential use of STI571 in other malignancies and the translation of this paradigm to other malignancies is explored...
  4. ncbi request reprint Imatinib: paradigm or anomaly?
    Brian J Druker
    Howard Hughes Medical Institute
    Cell Cycle 3:833-5. 2004
    ..Despite the success of imatinib, there remains much skepticism that this paradigm will be applicable to more complicated solid tumors. Whether this skepticism is appropriately deserved will be discussed...
  5. ncbi request reprint The role of the tyrosine kinase inhibitor STI571 in the treatment of cancer
    M E O'Dwyer
    Leukemia Program, Oregon Health Sciences University L592, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA
    Curr Cancer Drug Targets 1:49-57. 2001
    ..Future directions including the mechanisms and management of resistance and new therapeutic strategies are discussed. Finally, the literature supporting the use of STI571 in other malignancies, including solid tumors is briefly reviewed...
  6. ncbi request reprint David A. Karnofsky Award lecture. Imatinib as a paradigm of targeted therapies
    Brian J Druker
    Howard Hughe Medical Institute and Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    J Clin Oncol 21:239s-245s. 2003
  7. ncbi request reprint 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
    B J Druker
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    N Engl J Med 344:1038-42. 2001
    ....
  8. ncbi request reprint Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia
    B J Druker
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    N Engl J Med 344:1031-7. 2001
    ..Since tyrosine kinase activity is essential to the transforming function of BCR-ABL, an inhibitor of the kinase could be an effective treatment for CML...
  9. ncbi request reprint Inhibition of the Bcr-Abl tyrosine kinase as a therapeutic strategy for CML
    Brian J Druker
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, Oregon, OR 97239, USA
    Oncogene 21:8541-6. 2002
  10. ncbi request reprint Imatinib mesylate in the treatment of chronic myeloid leukaemia
    Brian J Druker
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Expert Opin Pharmacother 4:963-71. 2003
    ..For example, how durable will responses to imatinib mesylate be and is it necessary or possible to improve upon these results? Ongoing efforts to address these issues will be discussed...
  11. ncbi request reprint Imatinib and chronic myeloid leukemia: validating the promise of molecularly targeted therapy
    Brian J Druker
    Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97201, USA
    Eur J Cancer 38:S70-6. 2002
    ..The clinical development of imatinib illustrates the effectiveness of targeting molecular pathogenetic events. Hopefully, this example can be extended to other malignancies...
  12. ncbi request reprint Practical management of patients with chronic myeloid leukemia receiving imatinib
    Michael W N Deininger
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    J Clin Oncol 21:1637-47. 2003
    ..The treatment recommendations are intended to optimize therapy with imatinib while taking into account a patient's specific circumstances...
  13. doi request reprint Translation of the Philadelphia chromosome into therapy for CML
    Brian J Druker
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland, USA
    Blood 112:4808-17. 2008
    ..Continued studies of hematologic malignancies will allow this paradigm of targeting molecular pathogenetic events to be applied to many additional hematologic cancers...
  14. ncbi request reprint Molecularly targeted therapy: have the floodgates opened?
    Brian J Druker
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland, Oregon 97239, USA
    Oncologist 9:357-60. 2004
  15. ncbi request reprint Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib
    D W Sherbenou
    Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA
    Leukemia 21:489-93. 2007
    ..BCR-ABL-kinase domain mutations in patients with a stable CCR are infrequent, and their detection does not consistently predict relapse. Alternative mechanisms must be responsible for disease persistence in the majority of patients...
  16. ncbi request reprint Detection of ABL kinase domain mutations with denaturing high-performance liquid chromatography
    M W N Deininger
    Oregon Health and Science University Cancer Institute, Portland, OR 97201 L592, USA
    Leukemia 18:864-71. 2004
    ..Early detection of emerging mutant clones may aid in guiding decisions regarding alternative treatment options...
  17. ncbi request reprint STI571: targeting BCR-ABL as therapy for CML
    M J Mauro
    Leukemia Program, Division of Hematology and Medical Oncology, Oregon Health Sciences University, 3181 Sam Jackson Park Road, Portland, OR 97201, USA
    Oncologist 6:233-8. 2001
    ..Integration of STI571 into CML treatment algorithms will require long-term follow-up data from the ongoing phase II and III clinical studies...
  18. ncbi request reprint Chronic myelogenous leukaemia--new therapeutic principles
    B J Druker
    Leukaemia Program, Oregon Health Sciences University, Portland, OR, USA
    J Intern Med 250:3-9. 2001
    ..The results of clinical studies to date are highly encouraging and STI571 promises to be an important addition to the therapy of CML...
  19. ncbi request reprint ST1571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia: validating the promise of molecularly targeted therapy
    M J Mauro
    Leukemia Program, Oregon Health Sciences University, Portland 97201, USA
    Cancer Chemother Pharmacol 48:S77-8. 2001
    ..The results of clinical studies have demonstrated the potential of molecularly targeted therapies, and ST1571 is emerging as a new therapeutic agent for CML...
  20. ncbi request reprint Current treatment approaches for chronic myelogenous leukemia
    B J Druker
    Leukemia Program, Oregon Health Sciences University, Portland 97201, USA
    Cancer J 7:S14-8. 2001
    ..The clinical features, molecular pathogenesis, and current treatment options of CML are reviewed along with the development of STI571, the phase I clinical results, and the application of this paradigm to other malignancies...
  21. ncbi request reprint Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor
    M C Heinrich
    Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health Sciences University, and Portland Veterans Affairs Medical Center, USA
    Blood 96:925-32. 2000
    ..This compound may be useful in treating cancers associated with increased c-kit kinase activity...
  22. ncbi request reprint STI571: a gene product-targeted therapy for leukemia
    M J Mauro
    Leukemia Program, Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health Sciences University, OP28, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA
    Curr Oncol Rep 3:223-7. 2001
    ..Through rational drug development, STI571, a bcr-abl tyrosine kinase inhibitor, has emerged as a paradigm for gene product-targeted therapy, offering new hope for expanded treatment options for patients with CML...
  23. doi request reprint Characterization of BCR-ABL deletion mutants from patients with chronic myeloid leukemia
    D W Sherbenou
    Cell and Developmental Biology, Oregon Health and Science University, Portland, OR, USA
    Leukemia 22:1184-90. 2008
    ..Thus, it will be important to investigate the prognostic impact of coexpression of deletion mutants in CML patients during imatinib treatment...
  24. ncbi request reprint Chronic myelogenous leukemia
    M J Mauro
    Leukemia Program, Oregon Health Sciences University, Portland, Oregon, USA
    Curr Opin Oncol 13:3-7. 2001
    ..Through rational drug development, STI571, a bcr-abl tyrosine kinase inhibitor, has emerged as targeted therapy that offers new hope for expanded treatment options for patients with CML...
  25. ncbi request reprint A single nucleotide polymorphism in the coding region of ABL and its effects on sensitivity to imatinib
    L C Crossman
    Oregon Health and Science University Cancer Institute, Portland, OR, USA
    Leukemia 19:1859-62. 2005
    ..Clinicians should be aware that possession of the arginine allele of K247R does not reflect a mutation that necessitates a change in the therapeutic strategy, unless there are other signs of inadequate response to drug...
  26. ncbi request reprint Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukemia: a translational perspective
    P La Rosée
    Oregon Health and Science University, Division of Hematology and Medical Oncology, Portland 97201, USA
    Leukemia 16:1213-9. 2002
    ..Second, we analyze preliminary clinical data of ongoing combination studies. Finally, we provide a summary of approaches that use novel antileukemic agents with molecularly characterized modes of action...
  27. ncbi request reprint Demonstration of Philadelphia chromosome negative abnormal clones in patients with chronic myelogenous leukemia during major cytogenetic responses induced by imatinib mesylate
    M E O'Dwyer
    Division of Hematology and Ocology, Department of Medicine, Oregon Health and Science University, Portland 97201, USA
    Leukemia 17:481-7. 2003
    ..The presence of clonal abnormalities in Ph-negative cells of imatinib-treated CML patients with MCR and CHR highlights the importance of routine metaphase cytogenetic testing and long-term follow-up of all imatinib-treated patients...
  28. doi request reprint Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia
    Maynika V Rastogi
    Division of Pediatric Endocrinology, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239, USA
    Pediatr Blood Cancer 59:840-5. 2012
    ..This study details the growth phenotype of seven pediatric patients maintained in remission on imatnib mesylate over an extended period of time...
  29. ncbi request reprint Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia
    T Oda
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201
    J Biol Chem 269:22925-8. 1994
    ..A direct interaction between Crkl and Abl has also been shown using a yeast two-hybrid screen...
  30. doi request reprint Bruton's tyrosine kinase is not essential for Bcr-Abl-mediated transformation of lymphoid or myeloid cells
    M MacPartlin
    Center for Hematologic Malignancies, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Leukemia 22:1354-60. 2008
    ..Collectively this data argues against a critical role for BTK in Bcr-Abl-mediated leukemogenesis...
  31. ncbi request reprint The effect of prior exposure to imatinib on transplant-related mortality
    Michael Deininger
    Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR 97239, USA
    Haematologica 91:452-9. 2006
    ..Such patients may be eligible for allogeneic stem cell transplantation (SCT), raising the question whether imatinib therapy may compromise the outcome of subsequent SCT...
  32. ncbi request reprint Catalytic domains of tyrosine kinases determine the phosphorylation sites within c-Cbl
    A H Grossmann
    Department of Hematology and Medical Oncology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, L592 Portland, OR 97239, USA
    FEBS Lett 577:555-62. 2004
    ..Our data support the concept that SH1 domains determine the final sites of phosphorylation once PTKs reach their target proteins...
  33. ncbi request reprint CRKL binding to BCR-ABL and BCR-ABL transformation
    K S Kolibaba
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    Leuk Lymphoma 33:119-26. 1999
    ..These findings suggest both direct and indirect interactions of CRKL with BCR-ABL. Thus, disruption of the direct interaction with BCR-ABL has not excluded a role for CRKL in BCR-ABL-mediated transformation...
  34. ncbi request reprint Identification and characterization of two novel SH2 domain-containing proteins from a yeast two hybrid screen with the ABL tyrosine kinase
    T Oda
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    Oncogene 15:1255-62. 1997
    ..Shd was tyrosine phosphorylated in COS-7 cells co-transfected with Shd and c-Abl or Bcr-Abl. These results suggest that Shd may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system...
  35. ncbi request reprint Direct binding of CRKL to BCR-ABL is not required for BCR-ABL transformation
    C Heaney
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    Blood 89:297-306. 1997
    ..Thus, a direct interaction of CRKL and BCR-ABL is not required for CRKL to become tyrosine phosphorylated by BCR-ABL and suggests that CRKL function may still be required for BCR-ABL function through an indirect interaction...
  36. ncbi request reprint Activating alleles of JAK3 in acute megakaryoblastic leukemia
    Denise K Walters
    Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Cancer Cell 10:65-75. 2006
    ..These findings illustrate the biological importance of gain-of-function JAK3 mutations in leukemogenesis and demonstrate the utility of proteomic approaches to identifying clinically relevant mutations...
  37. pmc Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib
    Ian J Griswold
    Center for Hematologic Malignancies, Oregon Health and Science University, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Mol Cell Biol 26:6082-93. 2006
    ..The drug resistance and transformation potency of mutants may determine the outcome of patients on therapy with Abl kinase inhibitors...
  38. ncbi request reprint Circumventing resistance to kinase-inhibitor therapy
    Brian J Druker
    N Engl J Med 354:2594-6. 2006
  39. ncbi request reprint Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study
    Moshe Talpaz
    M D Anderson Cancer Center, Houston, Texas, USA
    Blood 99:1928-37. 2002
    ..Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity...
  40. pmc Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen: high efficacy of drug combinations
    Heather A Bradeen
    Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 108:2332-8. 2006
    ..However, sequencing uniformly revealed T315I, consistent with the need for a T315I inhibitor, to completely block resistance...
  41. ncbi request reprint Survival advantage from imatinib compared with the combination interferon-alpha plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials
    Lydia Roy
    Department of Oncology Hematology and Cell Therapy, EA 3805, CHU La Miletrie, 2 rue de la Miletrie, 86021 Poitiers Cedex, France
    Blood 108:1478-84. 2006
    ..In conclusion, within the limitation of this historical comparison, there is a survival advantage from first-line therapy with imatinib over IFN/Ara-C...
  42. ncbi request reprint Synergistic interactions between DMAG and mitogen-activated protein kinase kinase 1/2 inhibitors in Bcr/abl+ leukemia cells sensitive and resistant to imatinib mesylate
    Tri K Nguyen
    Department of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA
    Clin Cancer Res 12:2239-47. 2006
    ....
  43. ncbi request reprint Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies
    Marcus M Schittenhelm
    Department of Medicine, Division of Hematology Oncology, Oregon Health and Science University, Portland, USA
    Cancer Res 66:473-81. 2006
    ..Our studies suggest that dasatinib may have clinical efficacy against human neoplasms that are associated with gain-of-function KIT mutations...
  44. ncbi request reprint Targeted CML therapy: controlling drug resistance, seeking cure
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Curr Opin Genet Dev 16:92-9. 2006
    ..Together, these advances are contributing to a high level of disease control, and might ultimately lead to disease eradication...
  45. ncbi request reprint Low-level expression of proapoptotic Bcl-2-interacting mediator in leukemic cells in patients with chronic myeloid leukemia: role of BCR/ABL, characterization of underlying signaling pathways, and reexpression by novel pharmacologic compounds
    Karl J Aichberger
    Department of Internal Medicine I, Division of Hematology and Hemostaseology the Center of Excellence in Clinical and Experimental Oncology
    Cancer Res 65:9436-44. 2005
    ....
  46. pmc Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics
    Daniel J DeAngelo
    Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 108:3674-81. 2006
    ..Tandutinib at the MTD (525 mg twice daily) should be evaluated more extensively in patients with AML with FLT3-ITD mutations to better define its antileukemic activity...
  47. pmc Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic
    Junya Kuroda
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
    Proc Natl Acad Sci U S A 103:14907-12. 2006
    ..These results demonstrate that Bim and Bad account for most, perhaps all, imatinib-induced killing of Bcr/Abl+ leukemic cells and suggest previously undescribed drug combination strategies for cancer therapy...
  48. pmc Inhibition of polysome assembly enhances imatinib activity against chronic myelogenous leukemia and overcomes imatinib resistance
    Min Zhang
    Division of Hematology Oncology, Department of Medicine, University of California at Irvine, Irvine, California 92697, USA
    Mol Cell Biol 28:6496-509. 2008
    ..Together, this work supports the inhibition of translation initiation as a therapeutic strategy for treating cancers fueled by dysregulated translation...
  49. pmc Inhibition of p38 MAPK suppresses inflammatory cytokine induction by etoposide, 5-fluorouracil, and doxorubicin without affecting tumoricidal activity
    Collin R Elsea
    School of Nursing, Oregon Health and Science University, Portland, Oregon, United States of America
    PLoS ONE 3:e2355. 2008
    ..Activation of p38 MAPK mediated the drug's effects on inflammatory cytokine production in macrophages but not LLC1 cytotoxicity and this was confirmed with inhibitor studies...
  50. pmc Suppression of programmed cell death 4 (PDCD4) protein expression by BCR-ABL-regulated engagement of the mTOR/p70 S6 kinase pathway
    Nathalie Carayol
    Robert H Lurie Comprehensive Cancer Center and Division of Hematology Oncology, Northwestern University Medical School and Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60611, USA
    J Biol Chem 283:8601-10. 2008
    ..Altogether, our studies identify a novel mechanism by which BCR-ABL may promote leukemic cell growth, involving sequential engagement of the mTOR/p70 S6K pathway and downstream suppression of PDCD4 expression...
  51. ncbi request reprint Progressive loss of epidermal growth factor receptor in a subpopulation of breast cancers: implications in target-directed therapeutics
    Lee Yee Choong
    Oncology Research Institute, National University of Singapore, Singapore
    Mol Cancer Ther 6:2828-42. 2007
    ..Although no value of EGFR expression in prognosis was found, our findings are likely to have implications in the design of clinical trials targeting the EGFR family of proteins in breast cancer...
  52. pmc FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia
    Paolo Neviani
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA
    J Clin Invest 117:2408-21. 2007
    ..Altogether, these results highlight the therapeutic relevance of rescuing PP2A tumor suppressor activity in Ph1 leukemias and strongly support the introduction of the PP2A activator FTY720 in the treatment of CML-BC and Ph1 ALL patients...
  53. pmc Applying the discovery of the Philadelphia chromosome
    Daniel W Sherbenou
    Department of Cell and Developmental Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Clin Invest 117:2067-74. 2007
    ..The development of imatinib validates an emerging paradigm in cancer, in which a tumor is defined by genetic abnormalities and effective therapies are developed that target events critical to the growth and survival of a specific tumor...
  54. ncbi request reprint Lessons learned from the development of imatinib
    Nicholas B Lydon
    Leuk Res 28:S29-38. 2004
  55. ncbi request reprint Recent advancements in the treatment of chronic myelogenous leukemia
    Michael E O'Dwyer
    Leukemia Center, Oregon Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201, USA
    Annu Rev Med 53:369-81. 2002
    ..Through rational drug development, STI571, a Bcr-Abl tyrosine kinase inhibitor, has emerged as a paradigm for gene product targeted therapy, offering new hope for expanded treatment options for patients with CML...
  56. ncbi request reprint Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy
    Andreas Hochhaus
    III Medizinische Klinik, Medizinische Fakultat Mannheim, Universitat Heidelberg, Theodor Kutzer Ufer 1 3, 68167 Mannheim, Germany
    Blood 109:2303-9. 2007
    ..This trial was registered at www.clinicaltrials.gov as CA180013...
  57. ncbi request reprint Antileukemic activity of lysophosphatidic acid acyltransferase-beta inhibitor CT32228 in chronic myelogenous leukemia sensitive and resistant to imatinib
    Paul La Rosée
    Division of Hematology and Medical Oncology, Oregon Health and Sciences University, Portland, Oregon
    Clin Cancer Res 12:6540-6. 2006
    ..Inhibition of LPAAT-beta induces growth arrest and apoptosis in cancer cell lines, implicating LPAAT-beta as a potential drug target in neoplasia...
  58. pmc SHP-2 phosphatase is required for hematopoietic cell transformation by Bcr-Abl
    Jing Chen
    Department of Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106, USA
    Blood 109:778-85. 2007
    ..These studies identified a novel function of SHP-2 and suggest that SHP-2 might be a useful target for controlling Bcr-Abl-positive leukemias...
  59. ncbi request reprint BIRB-796 is not an effective ABL(T315I) inhibitor
    Thomas O'Hare
    Nat Biotechnol 23:1209-10; author reply 1210-1. 2005
  60. ncbi request reprint Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study
    Charles L Sawyers
    Department of Medicine and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Blood 99:3530-9. 2002
    ..Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs...
  61. ncbi request reprint Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
    George D Demetri
    Dana Farber Cancer Institute and Harvard Cancer Center, Boston, MA 02115, USA
    N Engl J Med 347:472-80. 2002
    ..Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors...
  62. ncbi request reprint Coexistence of phosphotyrosine-dependent and -independent interactions between Cbl and Bcr-Abl
    Isabelle Gaston
    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Ore 97239, USA
    Exp Hematol 32:113-21. 2004
    ..Following this initial interaction, Cbl can then become tyrosine phosphorylated and interact with the SH2 domain of Bcr-Abl, further stabilizing the complex...
  63. ncbi request reprint No correlation between the proliferative status of Bcr-Abl positive cell lines and the proapoptotic activity of imatinib mesylate (Gleevec/Glivec)
    Paul La Rosée
    Oregon Health and Science University Cancer Institute, Division of Hematology and Medical Oncology, Portland, Oregon 97239, USA
    Hematol J 4:413-9. 2003
    ..We conclude that resistance of primary CML cells that are insensitive to imatinib may be the result of molecular properties causing drug resistance rather than a consequence of quiescence itself...
  64. ncbi request reprint A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias
    Oliver G Ottmann
    Medizinische Klinik III Abteilung Haematologie, Johann Wolfgang Goethe Universitat, 60590 Frankfurt, Germany
    Blood 100:1965-71. 2002
    ..Further studies are warranted to test the effects of imatinib in combination with other agents and to define the mechanisms of resistance to imatinib...
  65. ncbi request reprint In vitro efficacy of combined treatment depends on the underlying mechanism of resistance in imatinib-resistant Bcr-Abl-positive cell lines
    Paul La Rosée
    Oregon Health and Science University Cancer Institute, Division of Hematology and Medical Oncology, Portland, OR 97239, USA
    Blood 103:208-15. 2004
    ..These data underline the importance of resistance testing and provide a rational approach for dose-adjusted administration of imatinib when combined with other agents...
  66. ncbi request reprint STI571 as a targeted therapy for CML
    Michael E O'Dwyer
    Leukemia Center, Oregon Health and Science University Cancer Institute, Portland, Oregon, USA
    Cancer Invest 21:429-38. 2003
    ..Thus, STI571 has emerged as a paradigm for gene product targeted therapy, offering expanded treatment options for patients with CML...
  67. ncbi request reprint Chronic myeloid leukemia following therapy with imatinib mesylate (Gleevec). Bone marrow histopathology and correlation with genetic status
    John L Frater
    Department of Pathology, Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Am J Clin Pathol 119:833-41. 2003
    ..Although all patients demonstrated an initial decrease in bone marrow cellularity after imatinib mesylate therapy, continued follow-up showed that histopathologic findings correlated with genetic response...
  68. ncbi request reprint Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571)
    Paul La Rosée
    Oregon Health and Sciences University Cancer Institute, Division of Hematology and Medical Oncology, Portland, Oregon 97239, USA
    Cancer Res 62:7149-53. 2002
    ....
  69. ncbi request reprint Quality of life in patients with newly diagnosed chronic phase chronic myeloid leukemia on imatinib versus interferon alfa plus low-dose cytarabine: results from the IRIS Study
    Elizabeth A Hahn
    Center on Outcomes, Research and Education, Evanston Northwestern Healthcare, 1001 University Pl, Ste 100, Evanston, IL 60201, USA
    J Clin Oncol 21:2138-46. 2003
    ..Quality of life (QOL) outcomes in patients with chronic myeloid leukemia (CML) were evaluated in an international phase III study...
  70. ncbi request reprint A functional genomics approach to Kaposi's sarcoma
    Ashlee V Moses
    Vaccine and Gene Therapy Institute and Department of Molecular Microbiology and Immunology, Oregon Health Science University, Portland, Oregon 97239, USA
    Ann N Y Acad Sci 975:180-91. 2002
    ..J. Virol. 76(16): 8383-8399). These data demonstrate that microarrays are useful for the identification of pharmacological targets essential for KS tumorigenesis...
  71. ncbi request reprint Overcoming resistance to imatinib by combining targeted agents
    Brian J Druker
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland, Oregon 97239, USA
    Mol Cancer Ther 2:225-6. 2003
  72. ncbi request reprint Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib
    Amie S Corbin
    Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 101:4611-4. 2003
    ..This study highlights the need for biochemical and biologic characterization, before a resistant phenotype can be ascribed to a mutant...
  73. ncbi request reprint The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML
    Michael E O'Dwyer
    Leukemia Center, Oregon Health and Science University Cancer Institute, Portland, USA
    Blood 100:1628-33. 2002
    ..Once patients have other signs of acceleration, clonal evolution predicts lower response rates and a shorter time to treatment failure...
  74. ncbi request reprint Divergent clinical outcome in two CML patients who discontinued imatinib therapy after achieving a molecular remission
    Michael J Mauro
    Center for Hematologic Malignancies, Oregon Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, UHN73C, Portland, OR 97239, USA
    Leuk Res 28:S71-3. 2004
    ....
  75. ncbi request reprint High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy
    Stephanie G Willis
    OHSU Cancer Institute, 3181 SW Sam Jackson Park Rd, Mailcode L592, Portland, OR 97239, USA
    Blood 106:2128-37. 2005
    ..KD mutants present at low levels do not invariably lead to relapse, and additional factors are required to induce a fully drug-resistant phenotype...
  76. ncbi request reprint In chronic myeloid leukemia white cells from cytogenetic responders and non-responders to imatinib have very similar gene expression signatures
    Lucy C Crossman
    Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Haematologica 90:459-64. 2005
    ..However, a subgroup of patients is refractory at the cytogenetic level. Clinically, it would be advantageous to identify such patients a priori, since they may benefit from more aggressive therapy...
  77. ncbi request reprint Identification of mTOR as a novel bifunctional target in chronic myeloid leukemia: dissection of growth-inhibitory and VEGF-suppressive effects of rapamycin in leukemic cells
    Matthias Mayerhofer
    Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Austria
    FASEB J 19:960-2. 2005
    ..In conclusion, rapamycin inhibits growth of CML cells in vitro and in vivo and, in addition, down-regulates expression of VEGF. Both effects may contribute to the antileukemic activity of the drug in CML...
  78. ncbi request reprint In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit
    Amie S Corbin
    Oregon Health and Science University, Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 106:227-34. 2005
    ..Thus, AP23464 and AP23848 potently and selectively target activation-loop mutants of Kit in vitro and in vivo and could have therapeutic potential against D816V-expressing malignancies...
  79. ncbi request reprint AMN107: tightening the grip of imatinib
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland, Oregon, 97239, USA
    Cancer Cell 7:117-9. 2005
    ..The implications of these results, and the potential role this and other novel ABL inhibitors may have in treating patients with CML, are discussed...
  80. pmc Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistance
    Ping Hui Tseng
    Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, 336 L M Parks Hall, Columbus, OH 43210, USA
    Blood 105:4021-7. 2005
    ..This synergistic action was, at least in part, mediated through the concerted effect on phospho-Akt. Together these data provide a novel therapeutic strategy to overcome imatinib mesylate resistance, especially with the Abl mutant T315I...
  81. ncbi request reprint Imatinib as a paradigm of targeted therapies
    Brian J Druker
    Howard Hughes Medical Institute, Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
    Adv Cancer Res 91:1-30. 2004
    ..Issues related to clinical trials of molecularly targeted agents are discussed, including patient and dose selection. Last, the translation of this paradigm to other malignancies is explored...
  82. ncbi request reprint SRCircumventing imatinib resistance
    Michael W N Deininger
    Oregon Health and Science University Cancer Institute, Center for Hematologic Malignancies, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Cancer Cell 6:108-10. 2004
    ..These studies demonstrate the importance and impact of conducting scientific studies as part of clinical trials...
  83. ncbi request reprint Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970
    Amie S Corbin
    Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 104:3754-7. 2004
    ..As phase 1 clinical trials of MLN518 in AML have shown little toxicity, our data suggest MLN518 is a promising candidate for the treatment of SM or AML with KIT mutations...
  84. ncbi request reprint Analysis of the structural basis of specificity of inhibition of the Abl kinase by STI571
    Amie S Corbin
    Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Biol Chem 277:32214-9. 2002
    ....
  85. ncbi request reprint In vitro studies of the combination of imatinib mesylate (Gleevec) and arsenic trioxide (Trisenox) in chronic myelogenous leukemia
    Paul La Rosée
    Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97201, USA
    Exp Hematol 30:729-37. 2002
    ..The aim of this study was the preclinical evaluation of imatinib mesylate (Gleevec, formerly STI571) in conjunction with arsenic trioxide (As2O3, Trisenox) for the treatment of chronic myelogenous leukemia (CML)...
  86. ncbi request reprint Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis
    Ian J Griswold
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland 97239, USA
    Blood 104:2912-8. 2004
    ..In analogy to imatinib mesylate in BCR-ABL-positive acute leukemia, MLN518-induced remissions may not be durable. Our studies provide the basis for integrating this compound into chemotherapy and transplantation protocols...
  87. ncbi request reprint Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia
    Stephen G O'Brien
    University of Newcastle, Newcastle, United Kingdom
    N Engl J Med 348:994-1004. 2003
    ..We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML...

Research Grants23

  1. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 2004
    ....
  2. Cancer and Kinases
    Brian Druker; Fiscal Year: 2005
    ..By facilitating the development of these drugs, we hope to improve the outcome for patients with cancer as rapidly as possible. ..
  3. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 2007
    ..Combined, these data should offer significant insights into the biology of and the mechanism of transformation by Bcr-Abl. ..
  4. OHSU Cancer Institute
    Brian Druker; Fiscal Year: 2007
    ..Many are now funded by the National Cancer Institute (NCI). ..
  5. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 2009
    ..Combined, these data should offer significant insights into the biology of and the mechanism of transformation by Bcr-Abl. ..
  6. CBL FUNCTION IN CELLULAR SIGNALING AND TRANSFORMATION
    Brian Druker; Fiscal Year: 2003
    ..Through these studies the investigators should gain a greater understanding of the contribution of tyrosine phosphorylation of Cbl to its function and the role of Cbl in myeloid transformation. ..
  7. CHRONIC MYELOGENOUS LEUKEMIA AND BCR-ABL SUBSTRATES
    Brian Druker; Fiscal Year: 1999
    ..Through these studies, it is hoped to be able to design specific therapeutic agents for the treatment of this disease. ..