Charles Sawyers

Summary

Affiliation: University of California
Country: USA

Publications

  1. 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
  2. ncbi request reprint Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia
    Charles L Sawyers
    Department of Medicine, Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles 90095, USA
    Cancer Cell 1:413-5. 2002
  3. ncbi request reprint Will mTOR inhibitors make it as cancer drugs?
    Charles L Sawyers
    Howard Hughes Medical Institute, Los Angeles, CA 90095, USA
    Cancer Cell 4:343-8. 2003
  4. ncbi request reprint Opportunities and challenges in the development of kinase inhibitor therapy for cancer
    Charles L Sawyers
    Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Genes Dev 17:2998-3010. 2003
  5. ncbi request reprint Disabling Abl-perspectives on Abl kinase regulation and cancer therapeutics
    Charles L Sawyers
    Department of Medicine, Molecular Biology Institute, UCLA School of Medicine, 90095, USA
    Cancer Cell 1:13-5. 2002
  6. ncbi request reprint Overview: the art of cancer drug screening: molecular target versus milieu-based screens
    Charles L Sawyers
    Department of Hematology Oncology, University of California, Los Angeles 90095, USA
    Curr Opin Investig Drugs 3:478-81. 2002
  7. ncbi request reprint Targeted cancer therapy
    Charles Sawyers
    Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, 10833 LeConte Avenue, Los Angeles, California 90095, USA
    Nature 432:294-7. 2004
  8. ncbi request reprint BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90
    Mercedes E Gorre
    Department of Medicine and Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, CA 900095 1678, USA
    Blood 100:3041-4. 2002
  9. ncbi request reprint Rational therapeutic intervention in cancer: kinases as drug targets
    Charles L Sawyers
    11 934 Factor Building, University of California, Los Angeles Division of Hematology and Oncology, 10833 Le Conte Avenue, Los Angeles, California 90095 1678, USA
    Curr Opin Genet Dev 12:111-5. 2002
  10. ncbi request reprint Molecular abnormalities in myeloid leukemias and myelodysplastic syndromes
    C L Sawyers
    Department of Medicine, University of California, Los Angeles 90095 1678, USA
    Leuk Res 22:1113-22. 1998

Detail Information

Publications68

  1. 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...
  2. ncbi request reprint Finding the next Gleevec: FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia
    Charles L Sawyers
    Department of Medicine, Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles 90095, USA
    Cancer Cell 1:413-5. 2002
    ..Activating mutations in the FLT3 receptor tyrosine kinase occur in 30% of patients with acute myeloid leukemia. Small molecule FLT3 kinase inhibitors show selective antitumor activity in preclinical models. Clinical studies are underway...
  3. ncbi request reprint Will mTOR inhibitors make it as cancer drugs?
    Charles L Sawyers
    Howard Hughes Medical Institute, Los Angeles, CA 90095, USA
    Cancer Cell 4:343-8. 2003
  4. ncbi request reprint Opportunities and challenges in the development of kinase inhibitor therapy for cancer
    Charles L Sawyers
    Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
    Genes Dev 17:2998-3010. 2003
  5. ncbi request reprint Disabling Abl-perspectives on Abl kinase regulation and cancer therapeutics
    Charles L Sawyers
    Department of Medicine, Molecular Biology Institute, UCLA School of Medicine, 90095, USA
    Cancer Cell 1:13-5. 2002
    ..New findings about Abl kinase domain regulation provide insight into novel strategies for targeted therapy...
  6. ncbi request reprint Overview: the art of cancer drug screening: molecular target versus milieu-based screens
    Charles L Sawyers
    Department of Hematology Oncology, University of California, Los Angeles 90095, USA
    Curr Opin Investig Drugs 3:478-81. 2002
  7. ncbi request reprint Targeted cancer therapy
    Charles Sawyers
    Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, 10833 LeConte Avenue, Los Angeles, California 90095, USA
    Nature 432:294-7. 2004
    ..Recent progress in understanding the molecular changes that underlie cancer development offer the prospect of specifically targeting malfunctioning molecules and pathways to achieve more effective and rational cancer therapy...
  8. ncbi request reprint BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90
    Mercedes E Gorre
    Department of Medicine and Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, CA 900095 1678, USA
    Blood 100:3041-4. 2002
    ..These data support clinical investigations of 17-AAG in imatinib mesylate-resistant Ph(+) leukemias...
  9. ncbi request reprint Rational therapeutic intervention in cancer: kinases as drug targets
    Charles L Sawyers
    11 934 Factor Building, University of California, Los Angeles Division of Hematology and Oncology, 10833 Le Conte Avenue, Los Angeles, California 90095 1678, USA
    Curr Opin Genet Dev 12:111-5. 2002
    ..These examples have galvanized the cancer research community to extend kinase-inhibitor therapy to other cancers...
  10. ncbi request reprint Molecular abnormalities in myeloid leukemias and myelodysplastic syndromes
    C L Sawyers
    Department of Medicine, University of California, Los Angeles 90095 1678, USA
    Leuk Res 22:1113-22. 1998
    ..Recent insights into the molecular basis of these leukemias is presented using selected examples from these groups...
  11. doi request reprint Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors
    Ronald L Paquette
    UCLA Department of Medicine, Los Angeles, CA, USA
    Cancer Genet 204:392-7. 2011
    ..Inhibition of c-ABL kinase-mediated DNA double-strand repair by TKIs may predispose to EVI1 translocation in this setting...
  12. pmc Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2
    X Wu
    Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 97:4233-8. 2000
    ..We propose that MAGI-2 improves the efficiency of PTEN signaling through assembly of a multiprotein complex at the cell membrane...
  13. pmc c-Abl is required for development and optimal cell proliferation in the context of p53 deficiency
    Y E Whang
    Department of Medicine, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 97:5486-91. 2000
    ..Inhibition of c-Abl function may be a therapeutic strategy to target p53-deficient cells selectively...
  14. ncbi request reprint Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification
    M E Gorre
    Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA
    Science 293:876-80. 2001
    ..These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance...
  15. pmc Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
    M S Neshat
    Department of Medicine, University of California School of Medicine, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 98:10314-9. 2001
    ..These results provide rationale for testing FRAP/mTOR inhibitors in PTEN null human cancers...
  16. ncbi request reprint Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3'-deoxy-3'-18F-fluorothymidine PET
    Christian Waldherr
    Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Center, David Geffen School of Medicine, University of California at Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA
    J Nucl Med 46:114-20. 2005
    ..The aim of this study was to evaluate, whether PET with (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) may be used to monitor noninvasively the antiproliferative effects of tyrosine kinase inhibitors...
  17. ncbi request reprint Dynamics of chronic myeloid leukaemia
    Franziska Michor
    Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, Massachusetts 02138, USA
    Nature 435:1267-70. 2005
    ..We calculate the probability of developing imatinib resistance mutations and estimate the time until detection of resistance. Our model provides the first quantitative insights into the in vivo kinetics of a human cancer...
  18. pmc Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases
    Todd A Carter
    Ambit, Inc, 4215 Sorrento Valley Boulevard, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 102:11011-6. 2005
    ....
  19. ncbi request reprint Calculated resistance in cancer
    Charles L Sawyers
    Nat Med 11:824-5. 2005
  20. ncbi request reprint Update on the use of imatinib mesylate
    Charles L Sawyers
    University of California, Los Angeles, 90095, USA
    Clin Adv Hematol Oncol 3:757-8. 2005
  21. ncbi request reprint Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer
    George V Thomas
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
    Nat Med 12:122-7. 2006
    ..Our findings provide preclinical rationale for prospective, biomarker-driven clinical studies of mTOR inhibitors in kidney cancer and suggest that FDG-PET scans may have use as a pharmacodynamic marker in this setting...
  22. ncbi request reprint Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer
    George V Thomas
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA
    Clin Cancer Res 10:8351-6. 2004
    ..Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited...
  23. ncbi request reprint HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stability
    Ingo K Mellinghoff
    Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
    Cancer Cell 6:517-27. 2004
    ..Surprisingly, the downstream signaling pathway responsible for these effects appears to involve kinases other than Akt. These data suggest that the HER2/ERBB3 pathway is a critical target in hormone-refractory prostate cancer...
  24. ncbi request reprint Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680
    Matthew A Young
    Departments of Molecular and Cell Biology and Chemistry, Howard Hughes Medical Institute, The University of California at Berkeley, Berkeley, CA 94720, USA
    Cancer Res 66:1007-14. 2006
    ....
  25. doi request reprint IkappaB kinase beta inhibition induces cell death in Imatinib-resistant and T315I Dasatinib-resistant BCR-ABL+ cells
    Elizabeth A Duncan
    Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7295, USA
    Mol Cancer Ther 7:391-7. 2008
    ..These data indicate that blockage of BCR-ABL-induced NF-kappaB activation via IkappaB kinase beta inhibition represents a potential new approach for treatment of Imatinib- or Dasatinib-resistant forms of chronic myelogenous leukemia...
  26. pmc Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma
    Tim F Cloughesy
    Department of Neurology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS Med 5:e8. 2008
    ..Small, molecularly focused clinical studies offer the promise of the early definition of optimal biologic dose and patient population...
  27. ncbi request reprint Cancer: mixing cocktails
    Charles L Sawyers
    Nature 449:993-6. 2007
  28. ncbi request reprint Where lies the blame for resistance--tumor or host?
    Charles L Sawyers
    Nat Med 13:1144-5. 2007
  29. pmc Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency
    Neil P Shah
    Division of Hematology Oncology, Department of Medicine, UCSF School of Medicine, San Francisco, California, USA
    J Clin Invest 117:2562-9. 2007
    ....
  30. pmc Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain
    Jeffrey C Lee
    Department of Medical Oncology and Center for Cancer Genome Discovery, Dana Farber Cancer Institute Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 3:e485. 2006
    ..Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy...
  31. pmc Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants
    Brian J Skaggs
    Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 103:19466-71. 2006
    ..Therefore, mutations that confer clinical resistance to kinase inhibitors can substantially alter kinase function and confer novel biological properties that may impact disease progression...
  32. ncbi request reprint Mammalian target of rapamycin inhibition promotes response to epidermal growth factor receptor kinase inhibitors in PTEN-deficient and PTEN-intact glioblastoma cells
    Maria Y Wang
    Department of Pathology and Laboratory Medicine, Henry E Singleton Brain Tumor Program, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California at Los Angeles, CA 90095 1732, USA
    Cancer Res 66:7864-9. 2006
    ..These studies provide strong rationale for combined mTOR/EGFR kinase inhibitor therapy in glioblastoma patients, particularly those with PTEN-deficient tumors...
  33. ncbi request reprint Treating imatinib-resistant leukemia: the next generation targeted therapies
    Michael R Burgess
    Molecular Biology Institute, Department of Medicine, The David Geffen School of Medicine, University of California, Los Angeles, USA
    ScientificWorldJournal 6:918-30. 2006
    ..This review focuses on the mechanisms of imatinib resistance and the strategies currently being developed to overcome clinical resistance...
  34. ncbi request reprint Will kinase inhibitors have a dark side?
    Charles L Sawyers
    Department of Medicine, University of California, Los Angeles, Los Angeles, USA
    N Engl J Med 355:313-5. 2006
  35. ncbi request reprint Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias
    Moshe Talpaz
    Department of Leukemia, M D Anderson Cancer Center, Houston, USA
    N Engl J Med 354:2531-41. 2006
    ..We evaluated dasatinib, a BCR-ABL inhibitor that targets most imatinib-resistant BCR-ABL mutations, in patients with chronic myelogenous leukemia (CML) or Ph-positive acute lymphoblastic leukemia (ALL)...
  36. ncbi request reprint Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment
    Su Chu
    Division of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA
    Blood 105:2093-8. 2005
    ..We conclude that BCR-ABL kinase mutations can be detected in CD34+ cells from CML patients in CCR on imatinib, may contribute to persistence of small populations of malignant progenitors, and could be a potential source of relapse...
  37. ncbi request reprint Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
    Catriona H M Jamieson
    Division of Hematology, Stanford University School of Medicine, Stanford, Calif 94305 5323, USA
    N Engl J Med 351:657-67. 2004
    ..In normal mouse hematopoietic stem cells, the process of self-renewal involves the beta-catenin-signaling pathway. We investigated whether leukemic stem cells in CML also use the beta-catenin pathway for self-renewal...
  38. ncbi request reprint Molecular mechanisms of resistance to STI571 in chronic myeloid leukemia
    Mercedes E Gorre
    Department of Medicine and Molecular Biology Institute, University of California, Los Angeles, California 90095 1678, USA
    Curr Opin Hematol 9:303-7. 2002
    ..Here the authors review recent work aimed at elucidating the nature of STI51 resistance...
  39. ncbi request reprint A novel pyridopyrimidine inhibitor of abl kinase is a picomolar inhibitor of Bcr-abl-driven K562 cells and is effective against STI571-resistant Bcr-abl mutants
    David R Huron
    Department of Medicine, Memorial Sloan Kettering Cancer Center and Program in Pharmacology, New York, New York 10021, USA
    Clin Cancer Res 9:1267-73. 2003
    ..PD166326 is a prototype of a new generation of anti-Bcr-abl compounds with picomolar potency and substantial activity against STI571-resistant mutants...
  40. ncbi request reprint Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment
    Ravi Bhatia
    Division of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA
    Blood 101:4701-7. 2003
    ..Patients in CCR with imatinib mesylate treatment need to be followed carefully to assess for risk of relapse...
  41. ncbi request reprint Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients: 14 months' experience
    Rita M Braziel
    Dept of Pathology, Oregon Health Sciences University, Portland, OR 97201, USA
    Blood 100:435-41. 2002
    ..Several patients acquired additional clonal cytogenetic abnormalities during therapy, a finding with significant implications for prognosis and laboratory monitoring in imatinib mesylate-treated CML patients...
  42. ncbi request reprint The emergence of resistance to targeted cancer therapeutics
    Ingo K Mellinghoff
    Departments of Medicine and Molecular Biology Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA
    Pharmacogenomics 3:603-23. 2002
    ..This article reviews the mechanisms of drug resistance to a variety of cancer therapeutics and provides an approach for how measures of drug target activity can be incorporated into clinical trial design...
  43. ncbi request reprint Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia
    Neil P Shah
    Department of Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Cancer Cell 2:117-25. 2002
    ..Multiple independent mutant clones were detected in a subset of relapsed cases. Our data support a clonal selection model of preexisting BCR-ABL mutations that confer imatinib resistance...
  44. ncbi request reprint Imatinib GIST keeps finding new indications: successful treatment of dermatofibrosarcoma protuberans by targeted inhibition of the platelet-derived growth factor receptor
    Charles L Sawyers
    J Clin Oncol 20:3568-9. 2002
  45. 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...
  46. pmc Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop
    Sergei Roumiantsev
    Center for Blood Research and Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115 5717, USA
    Proc Natl Acad Sci U S A 99:10700-5. 2002
    ..Because clinical resistance induced by the Y253F mutation might be overcome by dose escalation of STI-571, molecular genotyping of STI-571-resistant patients may provide information useful for rational therapeutic management...
  47. ncbi request reprint Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo
    Gheeyoung Choe
    Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA
    Cancer Res 63:2742-6. 2003
    ..These results provide the first dissection of the PI3K pathway in glioblastoma in vivo and suggest an approach to stratifying patients for targeted kinase inhibitor therapy...
  48. ncbi request reprint Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation
    Melissa S Holtz
    Division of Hematology and Bone Marrow Transplantation and the Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA 91010, USA
    Blood 99:3792-800. 2002
    ..These results suggest that inhibition of Bcr-Abl tyrosine kinase by imatinib mesylate restores normal hematopoiesis by removing the proliferative advantage of CML progenitors but that elimination of all CML progenitors may not occur...
  49. ncbi request reprint Myc-driven murine prostate cancer shares molecular features with human prostate tumors
    Katharine Ellwood-Yen
    Department of Medicine, and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Cancer Cell 4:223-38. 2003
    ..This approach illustrates how genomic technologies can be applied to mouse cancer models to guide evaluation of human tumor databases...
  50. ncbi request reprint Overriding imatinib resistance with a novel ABL kinase inhibitor
    Neil P Shah
    Division of Hematology and Oncology, Department of Medicine, The David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA
    Science 305:399-401. 2004
    ..These data illustrate how molecular insight into kinase inhibitor resistance can guide the design of second-generation targeted therapies...
  51. ncbi request reprint TORward AKTually useful mouse models
    Ingo K Mellinghoff
    Nat Med 10:579-80. 2004
  52. 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...
  53. ncbi request reprint Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias
    Neil P Shah
    Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    Oncogene 22:7389-95. 2003
    ..Additionally, genomic amplification of the BCR-ABL gene can occasionally be detected. This review will highlight mechanisms of STI571 resistance in clinical samples as well as preclinical models...
  54. ncbi request reprint AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression
    Joseph F Gera
    Department of Medicine, West Los Angeles Veteran s Administration UCLA Medical Center, University of California School of Medicine, Los Angeles, California 90073, USA
    J Biol Chem 279:2737-46. 2004
    ..These results identify two critical downstream molecular targets whose expression is regulated by AKT activity and whose down-regulation is required for rapamycin/CCI-779 sensitivity...
  55. ncbi request reprint The phosphatidylinositol 3-Kinase AKT pathway in human cancer
    Igor Vivanco
    Department of Medicine and Molecular Biology Institute, UCLA School of Medicine, 11 935 Factor Building, 10833 LeConte Avenue, Los Angeles, California 90095, USA
    Nat Rev Cancer 2:489-501. 2002
  56. pmc NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer
    Charlie D Chen
    Division of Hematology Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095 1678, USA
    Mol Cell Biol 22:2862-70. 2002
    ..These results suggest a role of NF-kappa B in prostate cancer progression...
  57. ncbi request reprint Nineteenth Annual Pezcoller Symposium: hypothesis-driven clinical investigation in cancer
    William G Kaelin
    Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Res 67:11102-5. 2007
    ..A session was devoted to the identification of markers of drug effectiveness. Two sessions were focused on opportunities for developing new specific molecular target-oriented therapies...
  58. doi request reprint The cancer biomarker problem
    Charles L Sawyers
    Howard Hughes Medical Institute, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA
    Nature 452:548-52. 2008
    ..One of the main barriers to further progress is identifying the biological indicators, or biomarkers, of cancer that predict who will benefit from a particular targeted therapy...
  59. pmc A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression
    Pradip K Majumder
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 14:146-55. 2008
    ..These data suggest that a p27(Kip1)-driven checkpoint limits progression of PIN to CaP...
  60. ncbi request reprint Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI-166 on human prostate cancer xenografts
    Ingo K Mellinghoff
    Department of Medicine, School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    Cancer Res 62:5254-9. 2002
    ..These results suggest that ErbB1/ErbB2 RTKs play an important role in the biology of androgen-independent prostate cancer and provide a rationale for clinical evaluation of inhibitors targeted to this pathway...
  61. ncbi request reprint Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors
    Ingo K Mellinghoff
    Department of Molecular and Medical Pharmacology and Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles 90095 1732, USA
    N Engl J Med 353:2012-24. 2005
    ..The mechanism of responsiveness of glioblastomas to these inhibitors is unknown...
  62. ncbi request reprint Amplification and overexpression of prosaposin in prostate cancer
    Shahriar Koochekpour
    Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
    Genes Chromosomes Cancer 44:351-64. 2005
    ....
  63. ncbi request reprint Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes
    Jung Hwa Kim
    Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151 742, South Korea
    Nature 434:921-6. 2005
    ....
  64. pmc Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance
    Michael R Burgess
    Molecular Biology Institute, Howard Hughes Medical Institute, and Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 102:3395-400. 2005
    ..The combination of imatinib plus BMS-354825 greatly reduced the recovery of drug-resistant clones. Our findings provide further rationale for considering kinase conformation in the design of kinase inhibitors against cancer targets...
  65. ncbi request reprint Molecular determinants of resistance to antiandrogen therapy
    Charlie D Chen
    Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA
    Nat Med 10:33-9. 2004
    ..These findings provide insight toward the design of new antiandrogens...
  66. ncbi request reprint Cross-species comparisons of cancer signaling
    Thomas G Graeber
    Nat Genet 37:7-8. 2005
  67. ncbi request reprint Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients
    Bin Peng
    Clinical Pharmacology, Novartis, One Health Plaza, Building 419, Room 2368, East Hanover, NJ 07936 1080, USA
    J Clin Oncol 22:935-42. 2004
    ..To evaluate the basic pharmacokinetic (PK) characteristics of imatinib mesylate and assess the relationship between the PK and pharmacodynamic (PD) properties of the drug...
  68. ncbi request reprint Context-dependent hormone-refractory progression revealed through characterization of a novel murine prostate cancer cell line
    Philip A Watson
    Division of Hematology Oncology, Department of Medicine, University of California at Los Angeles, 90095, USA
    Cancer Res 65:11565-71. 2005
    ....