Ellen Weisberg

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors
    Erik A Nelson
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 117:3421-9. 2011
  2. pmc Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cells
    Ellen Weisberg
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 8:e56473. 2013
  3. pmc Reversible resistance induced by FLT3 inhibition: a novel resistance mechanism in mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
    PLoS ONE 6:e25351. 2011
  4. doi request reprint Smac mimetics: implications for enhancement of targeted therapies in leukemia
    E Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Leukemia 24:2100-9. 2010
  5. doi request reprint Discovery and characterization of novel mutant FLT3 kinase inhibitors
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cancer Ther 9:2468-77. 2010
  6. doi request reprint Drug resistance in mutant FLT3-positive AML
    E Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Oncogene 29:5120-34. 2010
  7. pmc Discovery of a small-molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRalpha, Kit, and Src kinases: novel type II inhibitor of gatekeeper mutants
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA
    Blood 115:4206-16. 2010
  8. doi request reprint FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Drug Resist Updat 12:81-9. 2009
  9. doi request reprint Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Mol Cancer Ther 7:1121-9. 2008
  10. pmc Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity
    Ellen Weisberg
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Gastroenterology 131:1734-42. 2006

Detail Information

Publications32

  1. pmc The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors
    Erik A Nelson
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 117:3421-9. 2011
    ..Thus, targeting STAT5 may be an effective strategy for the treatment of CML and other myeloproliferative diseases...
  2. pmc Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cells
    Ellen Weisberg
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    PLoS ONE 8:e56473. 2013
    ..As a strategy to improve clinical efficacy, we searched for novel agents capable of potentiating the stroma-diminished effects of TKI treatment of mutant FLT3-expressing cells...
  3. pmc Reversible resistance induced by FLT3 inhibition: a novel resistance mechanism in mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
    PLoS ONE 6:e25351. 2011
    ..Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors...
  4. doi request reprint Smac mimetics: implications for enhancement of targeted therapies in leukemia
    E Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Leukemia 24:2100-9. 2010
    ..These results support the idea of using IAP inhibitors in conjunction with targeted tyrosine kinase inhibition to override drug resistance and suppress or eradicate residual disease...
  5. doi request reprint Discovery and characterization of novel mutant FLT3 kinase inhibitors
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cancer Ther 9:2468-77. 2010
    ..Thus, we present a structurally novel class of FLT3 inhibitors that warrants consideration for clinical testing against drug-resistant disease in AML patients...
  6. doi request reprint Drug resistance in mutant FLT3-positive AML
    E Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Oncogene 29:5120-34. 2010
    ....
  7. pmc Discovery of a small-molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRalpha, Kit, and Src kinases: novel type II inhibitor of gatekeeper mutants
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA
    Blood 115:4206-16. 2010
    ..The distinctive ability of HG-7-85-01 to simultaneously inhibit both wild-type and mutant forms of several kinases of clinical relevance is an important step in the development of the next generation of tyrosine kinase inhibitors...
  8. doi request reprint FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Drug Resist Updat 12:81-9. 2009
    ....
  9. doi request reprint Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Mol Cancer Ther 7:1121-9. 2008
    ..This in vitro system helped to elucidate stromal-secreted viability factors that may play a role in stromal-mediated cytoprotection of tyrosine kinase inhibitor-treated leukemia cells...
  10. pmc Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity
    Ellen Weisberg
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Gastroenterology 131:1734-42. 2006
    ..In this study, we compare the effects of 3 tyrosine kinase inhibitors, PKC412 and nilotinib, and imatinib, on 2 GIST-related PDGFRA mutants, V561D and D842V, which possess differential sensitivity to imatinib...
  11. pmc Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 111:3723-34. 2008
    ..Finally, BAG956 and rapamycin/RAD001 were shown to combine in a nonantagonistic fashion against BCR-ABL- and mutant FLT3-expressing cells both in vitro and in vivo...
  12. ncbi request reprint Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells
    Ellen Weisberg
    Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Mol Cancer Ther 6:1951-61. 2007
    ..Finally, the combination of LBW242 and PKC412 was sufficient to override stromal-mediated viability signaling conferring resistance to PKC412...
  13. ncbi request reprint Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Cell 7:129-41. 2005
    ..AMN107 is a promising new inhibitor for the therapy of CML and Ph+ ALL...
  14. pmc Development of 'DFG-out' inhibitors of gatekeeper mutant kinases
    Hwan Geun Choi
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Bioorg Med Chem Lett 22:5297-302. 2012
    ..Here we report on the 'hybrid design' concept and subsequent structure activity guided optimization efforts that resulted in the development of these inhibitors...
  15. pmc Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 109:2112-20. 2007
    ....
  16. pmc Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA, USA
    Blood 112:5161-70. 2008
    ..Thus, we present a novel class of FLT3 inhibitors that displays high selectivity and potency toward FLT3 as a molecular target, and which could potentially be used to override drug resistance in AML...
  17. ncbi request reprint NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma
    Laurence Catley
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Blood 102:2615-22. 2003
    ..Finally, a study using NVP-LAQ824 in a preclinical murine myeloma model provides in vivo relevance to our in vitro studies. Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in MM...
  18. ncbi request reprint Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412
    Ellen Weisberg
    Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Cell 1:433-43. 2002
    ..PKC412 is a potent inhibitor of mutant FLT3 and is a candidate for testing as an antileukemia agent in AML patients with mutant FLT3 receptors...
  19. pmc Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells
    Laurence Catley
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 108:3441-9. 2006
    ..These data confirm the potential clinical benefit of combining HDAC inhibitors with proteasome inhibitors, and provide insight into the mechanisms of synergistic anti-MM activity of bortezomib in combination with LBH589...
  20. ncbi request reprint Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia
    Ellen Weisberg
    Dana Farber Cancer Institute, Mayer 540, 44 Binney Street, Boston, MA 02115, USA
    Nat Rev Cancer 7:345-56. 2007
    ..Here, we describe the mechanism of action of imatinib in CML, the structural basis of imatinib resistance, and the potential of second-generation BCR-ABL inhibitors to circumvent resistance...
  21. ncbi request reprint Mutated tyrosine kinases as therapeutic targets in myeloid leukemias
    Martin Sattler
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Adv Exp Med Biol 532:121-40. 2003
    ..FLT3 tyrosine kinase inhibitors are currently being evaluated in clinical trials and may be very useful therapeutic agents in AML...
  22. pmc Combining the FLT3 inhibitor PKC412 and the triterpenoid CDDO-Me synergistically induces apoptosis in acute myeloid leukemia with the internal tandem duplication mutation
    Rehan Ahmad
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cancer Res 8:986-93. 2010
    ....
  23. ncbi request reprint Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML
    Jingrui Jiang
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, D720C, Boston, MA 02115, USA
    Blood 104:1855-8. 2004
    ..These results suggest that mutations at N841 represent a significant new activating mutation in patients with AML and that patients with such mutations may respond to small-molecule FLT3 inhibitors such as PKC412...
  24. ncbi request reprint Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer
    Nishit K Mukhopadhyay
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Ann Thorac Surg 81:1034-42. 2006
    ....
  25. pmc Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity
    Douglas W McMillin
    1 Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA 2 Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts, USA 3 Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 16:483-9. 2010
    ....
  26. ncbi request reprint PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRα-induced myeloproliferative disease
    Jan Cools
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 3:459-69. 2003
    ..Our data establish PKC412 as molecularly targeted therapy for HES and other diseases expressing activated PDGFRalpha and demonstrate the potential of alternative kinase inhibitors to overcome resistance in target tyrosine kinases...
  27. pmc The STAT5 Inhibitor Pimozide Displays Efficacy in Models of Acute Myelogenous Leukemia Driven by FLT3 Mutations
    Erik A Nelson
    Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women s Hospital, Boston, MA, USA
    Genes Cancer 3:503-11. 2012
    ..Therefore, identifying STAT5 inhibitors may provide a new avenue for the treatment of AML, and these may be effective alone or in combination with tyrosine kinase inhibitors...
  28. ncbi request reprint The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment
    Boris Lin
    Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 62:5019-26. 2002
    ..The demonstrated anti-MM activity of PTK787, coupled with its antiangiogenic effects, provides the framework for clinical trials of this agent to overcome drug resistance and improve outcome in MM...
  29. pmc Antileukemic Effects of Novel First- and Second-Generation FLT3 Inhibitors: Structure-Affinity Comparison
    Ellen Weisberg
    Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA, USA
    Genes Cancer 1:1021-32. 2010
    ....
  30. pmc An amino-indazole scaffold with spectrum selective kinase inhibition of FLT3, PDGFRα and kit
    Xianming Deng
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Bioorg Med Chem Lett 22:4579-84. 2012
    ..Several compounds such as 4 and 11 exhibit single-digit nanomolar EC(50)s against FLT3, c-Kit and the gatekeeper T674M mutant of PDGFRα...
  31. ncbi request reprint Resistance to imatinib (Glivec): update on clinical mechanisms
    Ellen Weisberg
    Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Drug Resist Updat 6:231-8. 2003
    ..Established mechanisms of resistance to imatinib are discussed, as are novel therapeutic approaches to improving drug responsiveness by reversing development of imatinib resistance in patients...
  32. ncbi request reprint Cloning and functional characterization of the murine mastermind-like 1 (Maml1) gene
    Lizi Wu
    Department of Medical Oncology, Mayer 540, Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Gene 328:153-65. 2004
    ..There seems to be close correlation of the spatial and temporal expression among Maml1, Notch1 and Hes1 in the central nervous system (CNS) during early development, implicating a role for the Maml1 gene in neurogenesis...