bortezomib

Summary

Summary: A pyrazine and boronic acid derivative that functions as a reversible PROTEASOME INHIBITOR. It is used as an ANTINEOPLASTIC AGENT in the treatment of MULTIPLE MYELOMA and MANTLE CELL LYMPHOMA.

Top Publications

  1. Terpos E, Christoulas D, Kokkoris P, Anargyrou K, Gavriatopoulou M, Migkou M, et al. Increased bone mineral density in a subset of patients with relapsed multiple myeloma who received the combination of bortezomib, dexamethasone and zoledronic acid. Ann Oncol. 2010;21:1561-2 pubmed publisher
  2. Wei J, Liu C, Ouyang H, Ma C, Xie M, Liu M, et al. Activation of RAGE/STAT3 pathway by methylglyoxal contributes to spinal central sensitization and persistent pain induced by bortezomib. Exp Neurol. 2017;296:74-82 pubmed publisher
    b>Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear...
  3. Hunter P. Not boring at all. Boron is the new carbon in the quest for novel drug candidates. EMBO Rep. 2009;10:125-8 pubmed publisher
  4. Attal M, Lauwers Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017;376:1311-1320 pubmed publisher
    ..However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation...
  5. Lu T, Gu M, Zhao Y, Zheng X, Xing C. Autophagy contributes to falcarindiol-induced cell death in breast cancer cells with enhanced endoplasmic reticulum stress. PLoS ONE. 2017;12:e0176348 pubmed publisher
    ..We also identified that FAD has synergistic effect with approved cancer drugs 5-FU and Bortezomib in killing breast cancer cells...
  6. Gilardini Montani M, Granato M, Santoni C, Del Porto P, Merendino N, D Orazi G, et al. Histone deacetylase inhibitors VPA and TSA induce apoptosis and autophagy in pancreatic cancer cells. Cell Oncol (Dordr). 2017;40:167-180 pubmed publisher
    ..VPA appears have a stronger and broader cytotoxic effect than TSA and, thus, may represent a better choice for anti-pancreatic cancer therapy. ..
  7. Laubach J, Moslehi J, Francis S, San Miguel J, Sonneveld P, Orlowski R, et al. A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for the treatment of multiple myeloma: towards providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma. Br J Haematol. 2017;178:547-560 pubmed publisher
    This retrospective analysis aimed to establish the overall cardiac safety profile of bortezomib using patient-level data from one phase 2 and seven phase 3 studies in previously untreated and relapsed/refractory multiple myeloma (MM)...
  8. Gambella M, Rocci A, Passera R, Gay F, Omede P, Crippa C, et al. High XBP1 expression is a marker of better outcome in multiple myeloma patients treated with bortezomib. Haematologica. 2014;99:e14-6 pubmed publisher
  9. Kumar S, Laubach J, Giove T, Quick M, Neuwirth R, Yung G, et al. Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. Br J Haematol. 2017;178:756-763 pubmed publisher
    Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing ..

More Information

Publications62

  1. Costa L, Abbas J, Ortiz Cruz K, Kang Y, Stuart R. Outcomes of patients with multiple myeloma and renal impairment treated with bortezomib, cyclophosphamide, and dexamethasone without plasma exchange. Eur J Haematol. 2012;89:432-4 pubmed publisher
  2. Wolf J, Siegel D, Goldschmidt H, Hazell K, Bourquelot P, Bengoudifa B, et al. Phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed/refractory multiple myeloma. Leuk Lymphoma. 2012;53:1820-3 pubmed publisher
  3. Bhende P, Park S, Lim M, Dittmer D, Damania B. The dual PI3K/mTOR inhibitor, NVP-BEZ235, is efficacious against follicular lymphoma. Leukemia. 2010;24:1781-4 pubmed publisher
  4. Siniscalchi A, Dentamaro T, Perrotti A, Tatangelo P, De Fabritiis P, Caravita T. Bortezomib-based therapy as induction regimen of an autograft program in front-line treatment of multiple myeloma with end-stage renal disease. Ann Hematol. 2010;89:821-2 pubmed publisher
  5. Fenichel M. FDA approves new agent for multiple myeloma. J Natl Cancer Inst. 2015;107:djv165 pubmed publisher
  6. Fröhlich K, Holle J, Aries P, Gross W, Moosig F. Successful use of bortezomib in a patient with systemic lupus erythematosus and multiple myeloma. Ann Rheum Dis. 2011;70:1344-5 pubmed publisher
  7. Eiamboonsert S, Salama Y, Watarai H, Dhahri D, Tsuda Y, Okada Y, et al. The role of plasmin in the pathogenesis of murine multiple myeloma. Biochem Biophys Res Commun. 2017;488:387-392 pubmed publisher
  8. Popat R, Plesner T, Davies F, Cook G, Cook M, Elliott P, et al. A phase 2 study of SRT501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma. Br J Haematol. 2013;160:714-7 pubmed publisher
  9. Mundt S, Basler M, Sawitzki B, Groettrup M. No prolongation of skin allograft survival by immunoproteasome inhibition in mice. Mol Immunol. 2017;88:32-37 pubmed publisher
    ..We conclude that inhibition of the immunoproteasome is not effective in prolonging skin allograft survival in skin allotransplantation. ..
  10. Olszewski A, Dusetzina S, Eaton C, Davidoff A, Trivedi A. Subsidies for Oral Chemotherapy and Use of Immunomodulatory Drugs Among Medicare Beneficiaries With Myeloma. J Clin Oncol. 2017;35:3306-3314 pubmed publisher
    ..and thalidomide) among beneficiaries with myeloma, who can receive either orally administered or parenteral (bortezomib-based) therapy...
  11. Morita R, Hashino S, Shirai S, Fujita N, Onozawa M, Kahata K, et al. Thrombotic microangiopathy after treatment with bortezomib and dexamethasone in a patient with multiple myeloma. Int J Hematol. 2008;88:248-250 pubmed publisher
  12. Ito R, Sato I, Tsujita T, Yokoyama A, Sugawara A. A ubiquitin-proteasome inhibitor bortezomib suppresses the expression of CYP11B2, a key enzyme of aldosterone synthesis. Biochem Biophys Res Commun. 2017;489:21-28 pubmed publisher
    ..We found that the ubiquitin-proteasome inhibitor bortezomib could suppress CYP11B2 expression and secretion of aldosterone induced by angiotensin II (Ang II) in ..
  13. Rosser A, Swallow G, Swann R, Chapman C. Salmonella enteritidis necrotising fasciitis in a multiple myeloma patient receiving bortezomib. Int J Hematol. 2010;91:149-51 pubmed publisher
  14. Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Rekhtman G, et al. Subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma: subanalysis of patients with renal impairment in the phase III MMY-3021 study. Haematologica. 2015;100:e207-10 pubmed publisher
  15. Xian M, Cao H, Cao J, Shao X, Zhu D, Zhang N, et al. Bortezomib sensitizes human osteosarcoma cells to adriamycin-induced apoptosis through ROS-dependent activation of p-eIF2?/ATF4/CHOP axis. Int J Cancer. 2017;141:1029-1041 pubmed publisher
    ..Here, we reported a potent combination therapy that bortezomib, a proteasome inhibitor, enhances adriamycin-induced apoptosis to eliminate osteosarcoma cells and we revealed ..
  16. Nogales Rincón O, Huerta Madrigal A, Merino Rodríguez B, Gonzalez Asanza C, Cos Arregui E, Menchén Fernández Pacheco P. Rectal bleeding and diarrhea caused by bortezomib-induced colitis. Gastroenterol Hepatol. 2010;33:753-4 pubmed publisher
  17. Russignan A, Spina C, Tamassia N, Cassaro A, Rigo A, Bagnato A, et al. Endothelin-1 receptor blockade as new possible therapeutic approach in multiple myeloma. Br J Haematol. 2017;178:781-793 pubmed publisher
    ..Interestingly, the combination of bosentan and the proteasome inhibitor bortezomib, currently approved for MM treatment, resulted in synergistic cytotoxic effects...
  18. Aguiar P, de Mendonça Lima T, Colleoni G, Storpirtis S. Efficacy and safety of bortezomib, thalidomide, and lenalidomide in multiple myeloma: An overview of systematic reviews with meta-analyses. Crit Rev Oncol Hematol. 2017;113:195-212 pubmed publisher
    This overview summarizes evidence for the efficacy and safety of bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma...
  19. Shuqing L, Jianmin Y, Chongmei H, Hui C, Wang J. Upregulated expression of the PSMB5 gene may contribute to drug resistance in patient with multiple myeloma when treated with bortezomib-based regimen. Exp Hematol. 2011;39:1117-8 pubmed publisher
  20. Bullova P, Cougnoux A, Marzouca G, Kopacek J, Pacak K. Bortezomib Alone and in Combination With Salinosporamid A Induces Apoptosis and Promotes Pheochromocytoma Cell Death In Vitro and in Female Nude Mice. Endocrinology. 2017;158:3097-3108 pubmed publisher
    ..are pharmaceutically available, we tested the first Food and Drug Administration-approved proteasome inhibitor bortezomib alone and in combination with another proteasome inhibitor, salinosporamid A, in pheochromocytoma cells...
  21. Yuan T, Zhang F, Yao Q, Liu Y, Zhu X, Wang X. Weekly versus biweekly bortezomib given in patients with indolent non-Hodgkin lymphoma: A meta-analysis. PLoS ONE. 2017;12:e0177950 pubmed publisher
    b>Bortezomib is recently studied as a novel agent in indolent lymphoma. The optimal schedule of bortezomib used in indolent lymphoma is still uncertain...
  22. Kropff M, Vogel M, Bisping G, Schlag R, Weide R, Knauf W, et al. Bortezomib and low-dose dexamethasone with or without continuous low-dose oral cyclophosphamide for primary refractory or relapsed multiple myeloma: a randomized phase III study. Ann Hematol. 2017;96:1857-1866 pubmed publisher
    ..controlled study aimed to evaluate the benefit of adding continuous low-dose oral cyclophosphamide to bortezomib-dexamethasone in patients with primary relapsed/refractory multiple myeloma...
  23. Ao N, Chen Q, Liu G. The Small Molecules Targeting Ubiquitin-Proteasome System for Cancer Therapy. Comb Chem High Throughput Screen. 2017;20:403-413 pubmed publisher
    ..Hence, UPS has become a popular target for developing chemotherapeutics against tumours. The application of bortezomib showed high efficiency in treating haematological malignancies by interfering with UPS activity...
  24. Dimopoulos M, Goldschmidt H, Niesvizky R, Joshua D, Chng W, Oriol A, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18:1327-1337 pubmed publisher
    ..reported to be significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone in an interim analysis...
  25. Wilck N, Fechner M, Dan C, Stangl V, Stangl K, Ludwig A. The Effect of Low-Dose Proteasome Inhibition on Pre-Existing Atherosclerosis in LDL Receptor-Deficient Mice. Int J Mol Sci. 2017;18: pubmed publisher
    ..Recently, low-dose proteasome inhibition with bortezomib has been shown to attenuate early atherosclerosis in low-density lipoprotein receptor-deficient (LDLR-/-
  26. Moreau P, Cavallo F, Leleu X, Hulin C, Amiot M, Descamps G, et al. Phase I study of the anti insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibody, AVE1642, as single agent and in combination with bortezomib in patients with relapsed multiple myeloma. Leukemia. 2011;25:872-4 pubmed publisher
  27. Stockler M, Wilcken N. Why is management of cancer pain still a problem?. J Clin Oncol. 2012;30:1907-8 pubmed publisher
  28. Stessman H, Lulla A, Xia T, Mitra A, Harding T, Mansoor A, et al. High-throughput drug screening identifies compounds and molecular strategies for targeting proteasome inhibitor-resistant multiple myeloma. Leukemia. 2014;28:2263-7 pubmed publisher
  29. Chan K, Filshie R, Nandurkar H, Quach H. Thrombotic microangiopathy complicating bortezomib-based therapy for multiple myeloma. Leuk Lymphoma. 2015;56:2185-6 pubmed publisher
  30. Schnerch D, Schuler J, Follo M, Felthaus J, Wider D, Klingner K, et al. Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest in AML in vitro and prolongs survival in vivo. Oncotarget. 2017;8:21153-21166 pubmed publisher
    ..We show that therapeutic doses of bortezomib block the slow degradation of cyclin B during a volasertib-induced mitotic arrest in AML cell lines and patient-..
  31. Hasinoff B, Patel D. Disulfiram is a slow-binding partial noncompetitive inhibitor of 20S proteasome activity. Arch Biochem Biophys. 2017;633:23-28 pubmed publisher
    ..of a slow-binding reaction, similar to that observed for the FDA-approved proteasomal-targeted anticancer drugs bortezomib and carfilzomib...
  32. Barosi G, Gattoni E, Guglielmelli P, Campanelli R, Facchetti F, Fisogni S, et al. Phase I/II study of single-agent bortezomib for the treatment of patients with myelofibrosis. Clinical and biological effects of proteasome inhibition. Am J Hematol. 2010;85:616-9 pubmed publisher
  33. Li J, Zhang W, Kang W, Cao X, Duan M, Zhou D. Bortezomib and dexamethasone as first-line therapy for a patient with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes syndrome complicated by renal failure. Leuk Lymphoma. 2012;53:2527-9 pubmed publisher
  34. Kim Y, Cho N, Cheon S, Kim K. Bortezomib, a proteasome inhibitor, alleviates atopic dermatitis by increasing claudin 1 protein expression. Biochem Biophys Res Commun. 2017;493:744-750 pubmed publisher
    ..In the present study, we investigated the role of bortezomib (BTZ) in the restoration of the reduced expression of claudin 1...
  35. Richardson P, Roy A, Acharyya S, Panneerselvam A, Mendelson E, Gunther A, et al. Treatment-free interval as a metric of patient experience and a health outcome of value for advanced multiple myeloma: the case for the histone deacetylase inhibitor panobinostat, a next-generation novel agent. Expert Rev Hematol. 2017;10:933-939 pubmed publisher
    ..The clinical health outcomes data from PANORAMA-1, the pivotal phase-3 trial comparing panobinostat-bortezomib-dexamethasone (PAN-BTZ-DEX) with placebo (PBO)-BTZ-DEX in RRMM patients treated with 1 to 3 prior regimens, ..
  36. Levacque Z, Rosales J, Lee K. Level of cdk5 expression predicts the survival of relapsed multiple myeloma patients. Cell Cycle. 2012;11:4093-5 pubmed publisher
  37. Lacognata C, Crimí F, Guolo A, Varin C, De March E, Vio S, et al. Diffusion-weighted whole-body MRI for evaluation of early response in multiple myeloma. Clin Radiol. 2017;72:850-857 pubmed publisher
    ..multiple myeloma who underwent whole-body MRI with diffusion-weighted imaging (DWI-MRI) before and after bortezomib-based induction chemotherapy were evaluated prospectively...
  38. Chen P, Yuan Q, Yang H, Wen X, You P, Hou D, et al. Homoharringtonine enhances bortezomib antimyeloma activity in myeloma cells adhesion to bone marrow stromal cells and in SCID mouse xenografts. Leuk Res. 2017;57:119-126 pubmed publisher
    Despite the great progress in the treatment, multiple myeloma (MM) still remains incurable. Bortezomib (BTZ), a reversible inhibitor of the 26S proteasome, is very effective against MM but unable to eradicate the MM cells in bone marrow ..
  39. Handa H, Kuroda Y, Kimura K, Masuda Y, Hattori H, Alkebsi L, et al. Long non-coding RNA MALAT1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma. Br J Haematol. 2017;179:449-460 pubmed publisher
    ..MALAT1 was significantly upregulated by bortezomib and doxorubicin...
  40. Kobayashi H, Miyagi N. HIV-negative plasmablastic lymphoma attaining sustained remission with bortezomib-combined dose-adjusted EPOCH therapy. Rinsho Ketsueki. 2017;58:443-448 pubmed publisher
    ..Treatment was initiated with dose-adjusted EPOCH added to a concurrent bortezomib regimen. After completion of four cycles, the patient achieved and sustained complete remission.
  41. Warlick E, Cao Q, Miller J. Bortezomib and vorinostat in refractory acute myelogenous leukemia and high-risk myelodysplastic syndromes: produces stable disease but at the cost of high toxicity. Leukemia. 2013;27:1789-91 pubmed publisher
  42. Stessman H, Mansoor A, Zhan F, Janz S, Linden M, Baughn L, et al. Reduced CXCR4 expression is associated with extramedullary disease in a mouse model of myeloma and predicts poor survival in multiple myeloma patients treated with bortezomib. Leukemia. 2013;27:2075-7 pubmed publisher
  43. Moreau P, de Wit E. Recent progress in relapsed multiple myeloma therapy: implications for treatment decisions. Br J Haematol. 2017;179:198-218 pubmed publisher
    ..The clinical data set is less well developed for the addition of a third agent to the combination of bortezomib and dexamethasone; nonetheless, data are presented supporting the addition of the histone deacetylase inhibitor ..
  44. Subedi A, Sharma L, Shah B. Bortezomib-induced acute congestive heart failure: a case report and review of literature. Ann Hematol. 2014;93:1797-9 pubmed publisher
  45. Abe N, Tomita T, Bohgaki M, Kasahara H, Koike T. Crystalglobulinemia manifesting as chronic arthralgia and acute limb ischemia: A clinical case report. Medicine (Baltimore). 2017;96:e6643 pubmed publisher
    ..Although he underwent above-knee amputation, he was treated with a bortezomib and dexamethasone-based chemotherapeutic regimen, following lenalidomide maintenance therapy...
  46. Becker P, Gooley T, Green D, Burwick N, Kim T, Kojouri K, et al. A phase 2 study of bortezomib, cyclophosphamide, pegylated liposomal doxorubicin and dexamethasone for newly diagnosed multiple myeloma. Blood Cancer J. 2016;6:e422 pubmed publisher
  47. Leleu X, Kyriakou C, Vande Broek I, Murphy P, Bacon P, Lewis P, et al. Prospective longitudinal study on quality of life in relapsed/refractory multiple myeloma patients receiving second- or third-line lenalidomide or bortezomib treatment. Blood Cancer J. 2017;7:e543 pubmed publisher
    ..and symptoms of patients with relapsed/refractory MM (RRMM) receiving second- or third-line lenalidomide or bortezomib treatment were measured in a prospective European multicentre, observational study at different time points...
  48. Powell C. Rounding up apoptosis resistance targets in lung cancer. Am J Respir Cell Mol Biol. 2009;41:7-8 pubmed publisher
  49. San Miguel J, Hungria V, Yoon S, Beksac M, Dimopoulos M, Elghandour A, et al. Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial. Br J Haematol. 2017;179:66-74 pubmed publisher
    Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (..
  50. Chen Y, Yeh M, Yu M, Wei Y, Chen W, Chen J, et al. Lapatinib-induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors. Breast Cancer Res. 2013;15:R108 pubmed publisher
    ..These findings suggest that combination therapy of a proteasome inhibitor with lapatinib may benefit TNBC patients. ..
  51. van der Helm L, Bosman M, Schuringa J, Vellenga E. Effective targeting of primitive AML CD34+ cells by the second-generation proteasome inhibitor carfilzomib. Br J Haematol. 2015;171:652-5 pubmed publisher
  52. Park G, Chung Y, Jeong J, Kim D. A p110?-specific inhibitor combined with bortezomib blocks drug resistance properties of EBV-related B cell origin cancer cells via regulation of NF-?B. Int J Oncol. 2017;50:1711-1720 pubmed publisher
    ..A combination of CAL-101, a p110?-specific inhibitor, with bortezomib treatment of HT/EBV cells synergistically suppressed proliferation, reduced levels of drug resistance-related ..
  53. Joly B, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129:2836-2846 pubmed publisher
    ..New drugs including N-acetylcysteine, bortezomib, recombinant ADAMTS13, and caplacizumab show promise in the management of TTP...