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Genomes and Genes | Ellen WeisbergSummaryAffiliation: Harvard University Country: USA Publications
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Publications
The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitorsErik 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...- Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cellsEllen 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... - Reversible resistance induced by FLT3 inhibition: a novel resistance mechanism in mutant FLT3-expressing cellsEllen 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... 
Smac mimetics: implications for enhancement of targeted therapies in leukemiaE 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...- Discovery and characterization of novel mutant FLT3 kinase inhibitorsEllen 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... - Drug resistance in mutant FLT3-positive AMLE Weisberg
Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Oncogene 29:5120-34. 2010.... - 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 mutantsEllen 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... - FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AMLEllen 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.... - Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cellsEllen 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... - Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivityEllen 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... - Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cellsEllen 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... 
Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cellsEllen 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...- Characterization of AMN107, a selective inhibitor of native and mutant Bcr-AblEllen 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... - Development of 'DFG-out' inhibitors of gatekeeper mutant kinasesHwan 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... - Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemiasEllen Weisberg
Dana Farber Cancer Institute, Boston, MA 02115, USA
Blood 109:2112-20. 2007.... - Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cellsEllen 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... - NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myelomaLaurence 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... - Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412Ellen 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... - Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cellsLaurence 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... - PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRalpha-induced myeloproliferative diseaseJan 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... - Combining the FLT3 inhibitor PKC412 and the triterpenoid CDDO-Me synergistically induces apoptosis in acute myeloid leukemia with the internal tandem duplication mutationRehan Ahmad
Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cancer Res 8:986-93. 2010.... - Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AMLJingrui 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... - Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemiaEllen 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... - Mutated tyrosine kinases as therapeutic targets in myeloid leukemiasMartin 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... - Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancerNishit K Mukhopadhyay
Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Ann Thorac Surg 81:1034-42. 2006.... - Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activityDouglas 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.... - The STAT5 Inhibitor Pimozide Displays Efficacy in Models of Acute Myelogenous Leukemia Driven by FLT3 MutationsErik 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... - The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironmentBoris 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... - Antileukemic Effects of Novel First- and Second-Generation FLT3 Inhibitors: Structure-Affinity ComparisonEllen Weisberg
Department of Medical Oncology Hematologic Neoplasia, Dana Farber Cancer Institute, Boston, MA, USA
Genes Cancer 1:1021-32. 2010.... - An amino-indazole scaffold with spectrum selective kinase inhibition of FLT3, PDGFRα and kitXianming 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... - Resistance to imatinib (Glivec): update on clinical mechanismsEllen 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... - Cloning and functional characterization of the murine mastermind-like 1 (Maml1) geneLizi 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...