Robert Orlowski

Summary

Affiliation: The University of Texas
Country: USA

Publications

  1. ncbi request reprint Targeting the proteasome as a therapeutic strategy against haematological malignancies
    Robert Z Orlowski
    Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Expert Opin Investig Drugs 15:117-30. 2006
  2. pmc Novel agents for multiple myeloma to overcome resistance in phase III clinical trials
    Robert Z Orlowski
    Department of Lymphoma Myeloma, and Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX Electronic address
    Semin Oncol 40:634-51. 2013
  3. pmc Why proteasome inhibitors cannot ERADicate multiple myeloma
    Robert Z Orlowski
    Department of Lymphoma Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Electronic address
    Cancer Cell 24:275-7. 2013
  4. pmc Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin
    Gabriele Buda
    Department of Oncology, Transplants and Advanced Technologies, University of Pisa, Pisa, Italy
    Ann Hematol 89:1133-40. 2010
  5. doi request reprint Proteasome inhibitors in cancer therapy: lessons from the first decade
    Robert Z Orlowski
    Department of Lymphoma Myeloma, Division of Cancer Medicine, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 14:1649-57. 2008
  6. doi request reprint International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)
    S Giralt
    Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M D Anderson Cancer Center, Houston, TX 77030 4009, USA
    Leukemia 23:1904-12. 2009
  7. ncbi request reprint Second generation proteasome inhibitors: carfilzomib and immunoproteasome-specific inhibitors (IPSIs)
    D J Kuhn
    The University of Texas M D Anderson Cancer Center, Department of Lymphoma and Myeloma, Division of Cancer Medicine, Houston, TX 77030 4009, USA
    Curr Cancer Drug Targets 11:285-95. 2011
  8. pmc Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitors
    Deborah J Kuhn
    Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 4009, USA
    Blood 113:4667-76. 2009
  9. pmc Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage--independent p53 phosphorylation in mantle cell lymphoma
    Richard J Jones
    Department of Lymphoma and Myeloma, University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4009, USA
    Clin Cancer Res 14:5416-25. 2008
  10. ncbi request reprint A Phase I study of bortezomib plus irinotecan in patients with advanced solid tumors
    David P Ryan
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
    Cancer 107:2688-97. 2006

Research Grants

Detail Information

Publications42

  1. ncbi request reprint Targeting the proteasome as a therapeutic strategy against haematological malignancies
    Robert Z Orlowski
    Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Expert Opin Investig Drugs 15:117-30. 2006
    ..The current state of knowledge about the activity of bortezomib, both alone and in combination with standard chemotherapeutics, as part of the emerging armamentarium against haematological malignancies is reviewed...
  2. pmc Novel agents for multiple myeloma to overcome resistance in phase III clinical trials
    Robert Z Orlowski
    Department of Lymphoma Myeloma, and Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX Electronic address
    Semin Oncol 40:634-51. 2013
    ..In addition, agents that are in phase II or III, potentially registration-enabling trials will be described as well, to provide an overview of the possible landscape in the relapsed and/or refractory arena over the next 5 years. ..
  3. pmc Why proteasome inhibitors cannot ERADicate multiple myeloma
    Robert Z Orlowski
    Department of Lymphoma Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Electronic address
    Cancer Cell 24:275-7. 2013
    ..In this issue of Cancer Cell, Leung-Hagesteijn and colleagues describe XBP1s(-) subpopulations of tumor cells that are resistant to bortezomib and may account for therapeutic failures in the clinic. ..
  4. pmc Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin
    Gabriele Buda
    Department of Oncology, Transplants and Advanced Technologies, University of Pisa, Pisa, Italy
    Ann Hematol 89:1133-40. 2010
    ..Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients...
  5. doi request reprint Proteasome inhibitors in cancer therapy: lessons from the first decade
    Robert Z Orlowski
    Department of Lymphoma Myeloma, Division of Cancer Medicine, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 14:1649-57. 2008
    ..This saga provides a salient example of the promise of translational medicine and a paradigm by which other agents may be successfully brought from the bench to the bedside...
  6. doi request reprint International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)
    S Giralt
    Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M D Anderson Cancer Center, Houston, TX 77030 4009, USA
    Leukemia 23:1904-12. 2009
    ..The panel was asked to discuss a variety of issues regarding stem cell collection and transplantation in myeloma especially with the arrival of plerixafor. Herein, is a summary of their deliberations and conclusions...
  7. ncbi request reprint Second generation proteasome inhibitors: carfilzomib and immunoproteasome-specific inhibitors (IPSIs)
    D J Kuhn
    The University of Texas M D Anderson Cancer Center, Department of Lymphoma and Myeloma, Division of Cancer Medicine, Houston, TX 77030 4009, USA
    Curr Cancer Drug Targets 11:285-95. 2011
    ..Herein, we discuss the preclinical and clinical development of carfilzomib and explore the potential of immunoproteasome-specific inhibitors, like IPSI-001, as a rational approach to exclusively target hematological malignancies...
  8. pmc Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitors
    Deborah J Kuhn
    Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 4009, USA
    Blood 113:4667-76. 2009
    ..These findings provide a rationale for the translation of IPSIs to the clinic, where they may provide antimyeloma activity with greater specificity and less toxicity than current inhibitors...
  9. pmc Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage--independent p53 phosphorylation in mantle cell lymphoma
    Richard J Jones
    Department of Lymphoma and Myeloma, University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4009, USA
    Clin Cancer Res 14:5416-25. 2008
    ..The ubiquitin-proteasome pathway has been validated as a target in non-Hodgkin's lymphoma through demonstration of the activity of the proteasome inhibitor bortezomib...
  10. ncbi request reprint A Phase I study of bortezomib plus irinotecan in patients with advanced solid tumors
    David P Ryan
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
    Cancer 107:2688-97. 2006
    ..The authors conducted a Phase I dose-finding trial to study the use of combined bortezomib plus irinotecan in patients with advanced solid tumors...
  11. ncbi request reprint The proteasome and proteasome inhibitors in cancer therapy
    Peter M Voorhees
    Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Annu Rev Pharmacol Toxicol 46:189-213. 2006
    ....
  12. ncbi request reprint Targeting the ubiquitin-proteasome pathway in breast cancer therapy
    E Claire Dees
    Department of Medicine, Division of Hematology Oncology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, USA
    Future Oncol 2:121-35. 2006
    ....
  13. pmc Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma
    Deborah J Kuhn
    Lineberger Comprehensive Cancer Center and Department of Medicine, Division of Hematology Oncology, University of North Carolina, Chapel Hill, NC, USA
    Blood 110:3281-90. 2007
    ..Carfilzomib also overcame resistance to other conventional agents and acted synergistically with dexamethasone to enhance cell death. Taken together, these data provide a rationale for the clinical evaluation of carfilzomib in MM...
  14. ncbi request reprint Bortezomib therapy following first relapse
    Robert Z Orlowski
    The Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill Chapel Hill, North Carolina, USA
    Oncology (Williston Park) 19:23-6. 2005
  15. ncbi request reprint Bortezomib and its role in the management of patients with multiple myeloma
    Robert Z Orlowski
    University of North Carolina at Chapel Hill, 22 003 Lineberger Comprehensive Cancer Center, CB 7295, Mason Farm Road, Chapel Hill, NC 27599 7295, USA
    Expert Rev Anticancer Ther 4:171-9. 2004
    ..Bortezomib may provide significant benefits to patients both alone and in combination with other agents and at several time points during the natural history of multiple myeloma...
  16. ncbi request reprint Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies
    Robert Z Orlowski
    Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Blood 105:3058-65. 2005
    ..Bortezomib/PegLD was safely administered in this study with promising antitumor activity, supporting further testing of this regimen...
  17. ncbi request reprint A phase 2 study of bortezomib in relapsed, refractory myeloma
    Paul G Richardson
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    N Engl J Med 348:2609-17. 2003
    ..Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity...
  18. ncbi request reprint Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression
    Robert Z Orlowski
    Department of Medicine, Division of Hematology Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    J Clin Oncol 25:3892-901. 2007
    ..This phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin (PLD) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma...
  19. doi request reprint Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy
    Pieter Sonneveld
    Department of Hematology, Erasmus Medical Center, Rotterdam, Netherlands
    Cancer 112:1529-37. 2008
    ....
  20. pmc Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy
    Qing Chen
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, USA
    Blood 111:4690-9. 2008
    ..These findings provide a rational framework for further development of SCF(Skp2) inhibitors as a novel class of antitumor agents...
  21. pmc The role of the ubiquitination-proteasome pathway in breast cancer: applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer
    Robert Z Orlowski
    The Department of Medicine, Division of Hematology Oncology, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA
    Breast Cancer Res 5:1-7. 2003
    ..Such drugs, alone and especially in combination with current chemotherapeutics, may well represent important advances in the therapy of patients with breast cancer...
  22. ncbi request reprint Clinical course of thrombocytopenia in patients treated with imatinib mesylate for accelerated phase chronic myelogenous leukemia
    Hendrik W van Deventer
    Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Rm 3009 Old Clinic Building, Chapel Hill, NC 27599 7305, USA
    Am J Hematol 71:184-90. 2002
    ..Grade III-IV thrombocytopenia is common in accelerated phase CML and may be a marker for the inability to achieve cytogenetic response using single agent imatinib mesylate...
  23. ncbi request reprint Bortezomib in recurrent and/or refractory multiple myeloma. Initial clinical experience in patients with impared renal function
    Sundar Jagannath
    Blood Stem Cell and Bone Marrow Transplantation, St Vincent s Comprehensive Cancer Center, New York, New York 10011 8202, USA
    Cancer 103:1195-200. 2005
    ..Bortezomib is a potent, reversible proteasome inhibitor that has been approved for the treatment of recurrent and/or refractory multiple myeloma, but its activity in patients with renal impairment has not been studied to date...
  24. ncbi request reprint Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies
    Robert Z Orlowski
    Lineberger Comprehensive Cancer Center, Department of Medicine, University of North Carolina at Chapel Hill, 27599 7295, USA
    J Clin Oncol 20:4420-7. 2002
    ..To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacodynamics (PD) of the proteasome inhibitor bortezomib (previously known as PS-341) in patients with refractory hematologic malignancies...
  25. ncbi request reprint NF-kappaB as a therapeutic target in cancer
    Robert Z Orlowski
    Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7295, USA
    Trends Mol Med 8:385-9. 2002
    ..However, as there is currently no drug that blocks specific NF-kappaB activation, conclusions drawn with small-molecule inhibitors must be interpreted carefully...
  26. ncbi request reprint Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer
    Sivagurunathan Somasundaram
    The Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Cancer Res 62:3868-75. 2002
    ....
  27. ncbi request reprint Evidence for involvement of calpain in c-Myc proteolysis in vivo
    George W Small
    The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Arch Biochem Biophys 400:151-61. 2002
    ..These studies support a role for calpain in the control of c-Myc levels in vivo, and suggest that mutations impacting on sensitivity to calpain may contribute to c-Myc-mediated tumorigenesis...
  28. ncbi request reprint Evidence that inhibition of p44/42 mitogen-activated protein kinase signaling is a factor in proteasome inhibitor-mediated apoptosis
    Robert Z Orlowski
    Lineberger Comprehensive Cancer Center and Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    J Biol Chem 277:27864-71. 2002
    ..These studies support a role for inactivation of signaling through the p44/42 MAPK pathway in proteasome inhibitor-mediated apoptosis...
  29. ncbi request reprint The proteasome as a target for cancer therapy
    Peter M Voorhees
    The Lineberger Comprehensive Cancer Center, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Clin Cancer Res 9:6316-25. 2003
    ..Below we discuss the rationale behind targeting the proteasome for cancer therapy, and review the preclinical and clinical data on proteasome inhibitors alone, and in combination with conventional chemotherapeutics...
  30. ncbi request reprint Emerging data on the use of anthracyclines in combination with bortezomib in multiple myeloma
    Peter M Voorhees
    Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, NC 27599, USA
    Clin Lymphoma Myeloma 7:S156-62. 2007
    ..Herein, we review the preclinical data supporting the use of bortezomib with anthracyclines and the promising clinical data with these combinations...
  31. ncbi request reprint Proteasome inhibitors in cancer therapy
    Robert Z Orlowski
    The Department of Medicine and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, USA
    Methods Mol Biol 301:339-50. 2005
    ....
  32. ncbi request reprint Phase II trial of neoadjuvant chemotherapy with docetaxel followed by epirubicin in stage II/III breast cancer
    Bhuvaneswari Ramaswamy
    Division of Hematology Oncology and Comprehensive Breast Health Services, Ohio State University Medical Center, Columbus, OH, USA
    Breast Cancer Res Treat 93:67-74. 2005
    ....
  33. ncbi request reprint A practical update on the use of bortezomib in the management of multiple myeloma
    Jesus San Miguel
    Hematology Department, Hospital Clinico Universitario de Salamanca, Servicio de Hematologia, Paseo de San Vicente 58, Salamanca E 37007, Spain
    Oncologist 11:51-61. 2006
    ..Information is given on the practical management of the most common adverse events, including peripheral neuropathy and thrombocytopenia, and the use of bortezomib in renal and hepatic impairment...
  34. ncbi request reprint Oral valacyclovir as prophylaxis against herpes simplex virus reactivation during high dose chemotherapy for leukemia
    Robert Z Orlowski
    The Sidney Kimmel Comprehensive Cancer Center, Divisions of Hematological Malignancies, Baltimore, Maryland 21287 8985, USA
    Leuk Lymphoma 45:2215-9. 2004
    ....
  35. ncbi request reprint Evidence that mitogen-activated protein kinase phosphatase-1 induction by proteasome inhibitors plays an antiapoptotic role
    George W Small
    The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Mol Pharmacol 66:1478-90. 2004
    ..Furthermore, they suggest that a proteasome inhibitor/anthracycline regimen holds potential for enhanced antitumor activity in part through repression of MKP-1, supporting clinical evaluation of such combinations...
  36. ncbi request reprint Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib
    Paul G Richardson
    Dana Farber Cancer Institute, Brigham and Women s Hospital, 44 Binney St, Dana 1B02, Boston, MA 02115, USA
    J Clin Oncol 24:3113-20. 2006
    ..To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma...
  37. ncbi request reprint Proteasome inhibitors induce a p38 mitogen-activated protein kinase (MAPK)-dependent anti-apoptotic program involving MAPK phosphatase-1 and Akt in models of breast cancer
    Yue Y Shi
    22 003 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB 7295, Mason Farm Road, Chapel Hill, NC 27599 7295, USA
    Breast Cancer Res Treat 100:33-47. 2006
    ..Further, they suggest that strategies targeting MKP-1 and Akt could enhance the anti-tumor efficacy of proteasome inhibitors against breast cancer...
  38. ncbi request reprint Emerging role of novel combinations for induction therapy in multiple myeloma
    Peter M Voorhees
    Department of Medicine, Division of Hematology Oncology, University of North Carolina at Chapel Hill, NC 27599 7305, USA
    Clin Lymphoma Myeloma 7:33-41. 2006
    ..Herein we review the early promising clinical activity of these regimens in patients with newly diagnosed MM...
  39. ncbi request reprint Bronchiolitis obliterans with organizing pneumonia after rituximab therapy for non-Hodgkin's lymphoma
    Suzanne E Biehn
    University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 7295, USA
    Hematol Oncol 24:234-7. 2006
    ..Physicians utilizing rituximab should be aware of this association given the difficulty of differentiating between presentations of BOOP and neoplastic pulmonary processes...
  40. pmc Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma
    Sagar Lonial
    Winship Cancer Institute, Emory University, Atlanta, GA, USA
    Blood 106:3777-84. 2005
    ..The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production...
  41. ncbi request reprint Mitogen-activated protein kinase phosphatase-1 is a mediator of breast cancer chemoresistance
    George W Small
    The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Cancer Res 67:4459-66. 2007
    ....
  42. ncbi request reprint Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myeloma
    Peter M Voorhees
    Division of Hematology Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7305, USA
    Clin Cancer Res 13:6469-78. 2007
    ....

Research Grants6

  1. Dual Proteasome and MAPK Inhibition in Cancer Therapy
    Robert Orlowski; Fiscal Year: 2007
    ..abstract_text> ..