Research Topics
Species | Robert OrlowskiSummaryAffiliation: The University of Texas Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Targeting the proteasome as a therapeutic strategy against haematological malignanciesRobert 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...
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 doxorubicinGabriele 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...
Proteasome inhibitors in cancer therapy: lessons from the first decadeRobert 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...- 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... - 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... - Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitorsDeborah 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... - Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage--independent p53 phosphorylation in mantle cell lymphomaRichard 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... - The proteasome and proteasome inhibitors in cancer therapyPeter 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.... - Targeting the ubiquitin-proteasome pathway in breast cancer therapyE 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.... - A Phase I study of bortezomib plus irinotecan in patients with advanced solid tumorsDavid 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... - Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myelomaDeborah 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... - Bortezomib therapy following first relapseRobert 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 - Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignanciesRobert 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... - A phase 2 study of bortezomib in relapsed, refractory myelomaPaul 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... - Bortezomib and its role in the management of patients with multiple myelomaRobert 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... - Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancerSivagurunathan 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.... - Emerging data on the use of anthracyclines in combination with bortezomib in multiple myelomaPeter 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... - The role of the ubiquitination-proteasome pathway in breast cancer: applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancerRobert 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... - 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 progressionRobert 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... - Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myelomaPeter 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.... - Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapyPieter Sonneveld
Department of Hematology, Erasmus Medical Center, Rotterdam, Netherlands
Cancer 112:1529-37. 2008.... - Evidence for involvement of calpain in c-Myc proteolysis in vivoGeorge 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... - Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagyQing 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... - Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignanciesRobert 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... - Clinical course of thrombocytopenia in patients treated with imatinib mesylate for accelerated phase chronic myelogenous leukemiaHendrik 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... - NF-kappaB as a therapeutic target in cancerRobert 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... - Mitogen-activated protein kinase phosphatase-1 is a mediator of breast cancer chemoresistanceGeorge 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.... - Bortezomib in recurrent and/or refractory multiple myeloma. Initial clinical experience in patients with impared renal functionSundar 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... - Oral valacyclovir as prophylaxis against herpes simplex virus reactivation during high dose chemotherapy for leukemiaRobert Z Orlowski
The Sidney Kimmel Comprehensive Cancer Center, Divisions of Hematological Malignancies, Baltimore, Maryland 21287 8985, USA
Leuk Lymphoma 45:2215-9. 2004.... - Proteasome inhibitors in cancer therapyRobert 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.... - Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myelomaSagar 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... - Phase II trial of neoadjuvant chemotherapy with docetaxel followed by epirubicin in stage II/III breast cancerBhuvaneswari 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..To our knowledge, this is first description of docetaxel-induced activation of mitogen-activated and stress-activated protein kinase pathways in human breast cancer... - A practical update on the use of bortezomib in the management of multiple myelomaJesus 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... - Evidence that mitogen-activated protein kinase phosphatase-1 induction by proteasome inhibitors plays an antiapoptotic roleGeorge 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... - The proteasome as a target for cancer therapyPeter 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... - Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomibPaul 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... - Proteasome inhibitors induce a p38 mitogen-activated protein kinase (MAPK)-dependent anti-apoptotic program involving MAPK phosphatase-1 and Akt in models of breast cancerYue 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... - Emerging role of novel combinations for induction therapy in multiple myelomaPeter 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... - Bronchiolitis obliterans with organizing pneumonia after rituximab therapy for non-Hodgkin's lymphomaSuzanne 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... - Evidence that inhibition of p44/42 mitogen-activated protein kinase signaling is a factor in proteasome inhibitor-mediated apoptosisRobert 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...
Research Grants
- Dual Proteasome and MAPK Inhibition in Cancer TherapyRobert Orlowski; Fiscal Year: 2007..abstract_text> ..