Thomas O'Hare

Summary

Affiliation: University of Utah
Country: USA

Publications

  1. pmc Threshold levels of ABL tyrosine kinase inhibitors retained in chronic myeloid leukemia cells determine their commitment to apoptosis
    Thomas O'Hare
    Division of Hematology and Hematologic Malignancies, University of Utah, Huntsman Cancer Institute, Salt Lake City, Utah, USA
    Cancer Res 73:3356-70. 2013
  2. pmc The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, USA
    Blood 118:5250-4. 2011
  3. doi request reprint Pushing the limits of targeted therapy in chronic myeloid leukaemia
    Thomas O'Hare
    Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, Utah 84112, USA
    Nat Rev Cancer 12:513-26. 2012
  4. 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
  5. 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
  6. pmc The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile
    Christopher A Eide
    Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA
    Cancer Res 71:3189-95. 2011
  7. doi request reprint KIT signaling governs differential sensitivity of mature and primitive CML progenitors to tyrosine kinase inhibitors
    Amie S Corbin
    Authors Affiliations OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon Howard Hughes Medical Institute, Chevy Chase, Maryland Huntsman Cancer Institute Division of Hematology and Hematologic Malignancies, The University of Utah, Salt Lake City, Utah Novartis Institutes for BioMedical Research, Basel, Switzerland and Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
    Cancer Res 73:5775-86. 2013
  8. 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
  9. ncbi request reprint New Bcr-Abl inhibitors in chronic myeloid leukemia: keeping resistance in check
    Thomas O'Hare
    Oregon Health and Science University Cancer Institute, Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Expert Opin Investig Drugs 17:865-78. 2008
  10. pmc A BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice
    Kara J Johnson
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, United States of America
    PLoS ONE 4:e7439. 2009

Collaborators

Detail Information

Publications25

  1. pmc Threshold levels of ABL tyrosine kinase inhibitors retained in chronic myeloid leukemia cells determine their commitment to apoptosis
    Thomas O'Hare
    Division of Hematology and Hematologic Malignancies, University of Utah, Huntsman Cancer Institute, Salt Lake City, Utah, USA
    Cancer Res 73:3356-70. 2013
    ..These studies refine our understanding of apoptotic commitment in CML cells and highlight parameters important to design of therapeutic kinase inhibitors for CML and other malignancies...
  2. pmc The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, USA
    Blood 118:5250-4. 2011
    ....
  3. doi request reprint Pushing the limits of targeted therapy in chronic myeloid leukaemia
    Thomas O'Hare
    Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, Utah 84112, USA
    Nat Rev Cancer 12:513-26. 2012
    ....
  4. 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...
  5. 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...
  6. pmc The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile
    Christopher A Eide
    Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA
    Cancer Res 71:3189-95. 2011
    ..Taken together, these findings support continued evaluation of DCC-2036 as an important new agent for treatment-refractory CML...
  7. doi request reprint KIT signaling governs differential sensitivity of mature and primitive CML progenitors to tyrosine kinase inhibitors
    Amie S Corbin
    Authors Affiliations OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon Howard Hughes Medical Institute, Chevy Chase, Maryland Huntsman Cancer Institute Division of Hematology and Hematologic Malignancies, The University of Utah, Salt Lake City, Utah Novartis Institutes for BioMedical Research, Basel, Switzerland and Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
    Cancer Res 73:5775-86. 2013
    ....
  8. 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...
  9. ncbi request reprint New Bcr-Abl inhibitors in chronic myeloid leukemia: keeping resistance in check
    Thomas O'Hare
    Oregon Health and Science University Cancer Institute, Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Expert Opin Investig Drugs 17:865-78. 2008
    ..Improved Abl inhibitor therapies will be useful in achieving maximum disease control but a clinical T315I inhibitor remains a high priority...
  10. pmc A BCR-ABL mutant lacking direct binding sites for the GRB2, CBL and CRKL adapter proteins fails to induce leukemia in mice
    Kara J Johnson
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, United States of America
    PLoS ONE 4:e7439. 2009
    ..Our data suggest that inhibition of BCR-ABL-induced leukemia by disrupting protein interactions could be possible, but would require blocking of multiple sites...
  11. pmc Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis
    Jennifer L Snead
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Blood 114:3459-63. 2009
    ..Furthermore, they challenge the widely held notion that continuous target inhibition is required for optimal efficacy of kinase inhibitors...
  12. pmc Absence of SKP2 expression attenuates BCR-ABL-induced myeloproliferative disease
    Anupriya Agarwal
    Division of Hematology and Oncology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 112:1960-70. 2008
    ..Hence, stabilization of p27 by inhibiting its recognition by SCF(SKP2) may be therapeutically useful...
  13. pmc RNAi screen for rapid therapeutic target identification in leukemia patients
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Proc Natl Acad Sci U S A 106:8695-700. 2009
    ..Combination of this technique with whole-genome sequencing will represent an ideal tool for oncogenic target identification such that specific therapies can be matched with individual patients...
  14. 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...
  15. 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...
  16. pmc BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML: frequency and clonal relationships
    Jamshid S Khorashad
    Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT 84112, USA
    Blood 121:489-98. 2013
    ....
  17. pmc SGX393 inhibits the CML mutant Bcr-AblT315I and preempts in vitro resistance when combined with nilotinib or dasatinib
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Proc Natl Acad Sci U S A 105:5507-12. 2008
    ..These findings suggest that combination of a T315I inhibitor with the current clinically used inhibitors may be useful for reduction of Bcr-Abl mutants in Philadelphia chromosome-positive leukemia...
  18. pmc AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Cancer Cell 16:401-12. 2009
    ..Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML...
  19. doi request reprint Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, Oregon, USA
    Clin Cancer Res 17:212-21. 2011
    ....
  20. pmc RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, USA
    Blood 111:2238-45. 2008
    ..This technique, with additional development, might eventually offer the potential to match specific therapies with individual patients based on a functional assay...
  21. pmc TNF╬▒ facilitates clonal expansion of JAK2V617F positive cells in myeloproliferative neoplasms
    Angela G Fleischman
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR, USA
    Blood 118:6392-8. 2011
    ....
  22. ncbi request reprint Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 104:2532-9. 2004
    ..The potency of AP23464 against imatinib mesylate-refractory Bcr-Abl and its distinct binding mode relative to imatinib mesylate warrant further investigation of AP23464 for the treatment of CML...
  23. doi request reprint New strategies for the first-line treatment of chronic myeloid leukemia: can resistance be avoided?
    Jennifer L Snead
    Oregon Health and Science University Cancer Institute, Portland, OR, USA
    Clin Lymphoma Myeloma 8:S107-17. 2008
    ..Herein, we review current and emerging paradigms for using Abl kinase inhibitors to achieve maximal disease control and strategies to eradicate disease by targeting leukemic stem cells...
  24. pmc Kinase pathway dependence in primary human leukemias determined by rapid inhibitor screening
    Jeffrey W Tyner
    Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA
    Cancer Res 73:285-96. 2013
    ..Taken together, our results suggested that drug target scores derived from a comprehensive kinase inhibitor panel could predict pathway dependence in cancer cells while simultaneously identifying potential therapeutic options...
  25. doi request reprint Single particle quantum dot imaging achieves ultrasensitive detection capabilities for Western immunoblot analysis
    Benjamin Scholl
    Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239, USA
    ACS Nano 3:1318-28. 2009
    ....