{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:47:09Z","timestamp":1791298029897,"version":"4.1.0"},"reference-count":147,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"Abstract<\/jats:title>\n The destruction of proteins via the ubiquitin\u2013proteasome system is a multi-step, complex process involving polyubiquitination of substrate proteins, followed by proteolytic degradation by the macromolecular 26S proteasome complex. Inhibitors of the proteasome promote the accumulation of proteins that are deleterious to cell survival, and represent promising anti-cancer agents. In multiple myeloma and mantle cell lymphoma, treatment with the first-generation proteasome inhibitor, bortezomib, or the second-generation inhibitor, carfilzomib, has demonstrated significant therapeutic benefit in humans. This has prompted United States Food and Drug Administration (US FDA) approval of these agents and development of additional second-generation compounds with improved properties. There is considerable interest in extending the benefits of proteasome inhibitors to the treatment of solid tumor malignancies. Herein, we review progress that has been made in the preclinical development and clinical evaluation of different proteasome inhibitors in solid tumors. In addition, we describe several novel approaches that are currently being pursued for the treatment of solid tumors, including drug combinatorial strategies incorporating proteasome inhibitors and the targeting of components of the ubiquitin\u2013proteasome system that are distinct from the 26S proteasome complex.<\/jats:p>","DOI":"10.1530\/erc-14-0005","type":"journal-article","created":{"date-parts":[[2014,3,22]],"date-time":"2014-03-22T01:41:05Z","timestamp":1395452465000},"page":"T1-T17","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":82,"title":["The ubiquitin\u2013proteasome system: opportunities for therapeutic intervention in solid tumors"],"prefix":"10.1530","volume":"22","author":[{"given":"Daniel E","family":"Johnson","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology","department":["Departments of Medicine, and Pharmacology and Chemical Biology, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Room 2.18c, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, Pennsylvania 15213, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2026070909024517100_bib1","unstructured":"Aggarwal\n BB\n \n \n 2004\n Nuclear factor-\u03baB: the enemy within. Cancer Cell6203\u2013208. (doi:10.1016\/j.ccr.2004.09.003)."},{"key":"2026070909024517100_bib2","doi-asserted-by":"crossref","unstructured":"Aghajanian\n C\n \n \n Blessing\n JA\n \n \n Darcy\n KM\n \n \n Reid\n G\n \n \n DeGeest\n K\n \n \n Rubin\n SC\n \n \n Mannel\n RS\n \n \n Rotmensch\n J\n \n \n Schilder\n RJ\n \n \n Riordan\n W\n \n \n \n 2009\n A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecologic Oncology115215\u2013220. (doi:10.1016\/j.ygyno.2009.07.023).","DOI":"10.1016\/j.ygyno.2009.07.023"},{"key":"2026070909024517100_bib3","doi-asserted-by":"crossref","unstructured":"Allen\n C\n \n \n Saigal\n K\n \n \n Nottingham\n L\n \n \n Arun\n P\n \n \n Chen\n Z\n \n \n Van Waes\n C\n \n \n 2008\n Bortezomib-induced apoptosis with limited clinical response is accompanied by inhibition of canonical but not alternative nuclear factor-{\u03ba}B subunits in head and neck cancer. Clinical Cancer Research144175\u20134185. (doi:10.1158\/1078-0432.CCR-07-4470).","DOI":"10.1158\/1078-0432.CCR-07-4470"},{"key":"2026070909024517100_bib4","doi-asserted-by":"crossref","unstructured":"Arastu-Kapur\n S\n \n \n Anderl\n JL\n \n \n Kraus\n M\n \n \n Parlati\n F\n \n \n Shenk\n KD\n \n \n Lee\n SJ\n \n \n Muchamuel\n T\n \n \n Bennett\n MK\n \n \n Driessen\n C\n \n \n Ball\n AJ\n \n \n \n 2011\n Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clinical Cancer Research172734\u20132743. (doi:10.1158\/1078-0432.CCR-10-1950).","DOI":"10.1158\/1078-0432.CCR-10-1950"},{"key":"2026070909024517100_bib5","doi-asserted-by":"crossref","unstructured":"Argiris\n A\n \n \n Duffy\n AG\n \n \n Kummar\n S\n \n \n Simone\n NL\n \n \n Arai\n Y\n \n \n Kim\n SW\n \n \n Rudy\n SF\n \n \n Kannabiran\n VR\n \n \n Yang\n X\n \n \n Jang\n M\n \n \n \n 2011\n Early tumor progression associated with enhanced EGFR signaling with bortezomib, cetuximab, and radiotherapy for head and neck cancer. Clinical Cancer Research175755\u20135764. (doi:10.1158\/1078-0432.CCR-11-0861).","DOI":"10.1158\/1078-0432.CCR-11-0861"},{"key":"2026070909024517100_bib6","unstructured":"Asklund\n T\n \n \n Kvarnbrink\n S\n \n \n Holmlund\n C\n \n \n Wibom\n C\n \n \n Bergenheim\n T\n \n \n Henriksson\n R\n \n \n Hedman\n H\n \n \n 2012\n Synergistic killing of glioblastoma stem-like cells by bortezomib and HDAC inhibitors. Anticancer Research322407\u20132413."},{"key":"2026070909024517100_bib7","doi-asserted-by":"crossref","unstructured":"Bai\n J\n \n \n Demirjian\n A\n \n \n Sui\n J\n \n \n Marasco\n W\n \n \n Callery\n MP\n \n \n 2006\n Histone deacetylase inhibitor trichostatin A and proteasome inhibitor PS-341 synergistically induce apoptosis in pancreatic cancer cells. Biochemical and Biophysical Research Communications3481245\u20131253. (doi:10.1016\/j.bbrc.2006.07.185).","DOI":"10.1016\/j.bbrc.2006.07.185"},{"key":"2026070909024517100_bib8","unstructured":"Balz\n V\n \n \n Scheckenbach\n K\n \n \n Gotte\n K\n \n \n Bockmuhl\n U\n \n \n Petersen\n I\n \n \n Bier\n H\n \n \n 2003\n Is the p53 inactivation frequency in squamous cell carcinomas of the head and neck underestimated? Analysis of p53 exons 2\u201311 and human papillomavirus 16\/18 E6 transcripts in 123 unselected tumor specimens. Cancer Research631188\u20131191."},{"key":"2026070909024517100_bib9","doi-asserted-by":"crossref","unstructured":"Basler\n M\n \n \n Kirk\n CJ\n \n \n Groettrup\n M\n \n \n 2013\n The immunoproteasome in antigen processing and other immunological functions. Current Opinion in Immunology2574\u201380. (doi:10.1016\/j.coi.2012.11.004).","DOI":"10.1016\/j.coi.2012.11.004"},{"key":"2026070909024517100_bib10","doi-asserted-by":"crossref","unstructured":"Bazzaro\n M\n \n \n Lin\n Z\n \n \n Santillan\n A\n \n \n Lee\n MK\n \n \n Wang\n MC\n \n \n Chan\n KC\n \n \n Bristow\n RE\n \n \n Mazitschek\n R\n \n \n Bradner\n J\n \n \n Roden\n RB\n \n \n 2008\n Ubiquitin proteasome system stress underlies synergistic killing of ovarian cancer cells by bortezomib and a novel HDAC6 inhibitor. Clinical Cancer Research147340\u20137347. (doi:10.1158\/1078-0432.CCR-08-0642).","DOI":"10.1158\/1078-0432.CCR-08-0642"},{"key":"2026070909024517100_bib11","doi-asserted-by":"crossref","unstructured":"Belloni\n D\n \n \n Veschini\n L\n \n \n Foglieni\n C\n \n \n Dell'Antonio\n G\n \n \n Caligaris-Cappio\n F\n \n \n Ferrarini\n M\n \n \n Ferrero\n E\n \n \n 2010\n Bortezomib induces autophagic death in proliferating human endothelial cells. Experimental Cell Research3161010\u20131018. (doi:10.1016\/j.yexcr.2009.11.005).","DOI":"10.1016\/j.yexcr.2009.11.005"},{"key":"2026070909024517100_bib12","doi-asserted-by":"crossref","unstructured":"Berenson\n JR\n \n \n Matous\n J\n \n \n Swift\n RA\n \n \n Mapes\n R\n \n \n Morrison\n B\n \n \n Yeh\n HS\n \n \n 2007\n A phase I\/II study of arsenic trioxide\/bortezomib\/ascorbic acid combination therapy for the treatment of relapsed or refractory multiple myeloma. Clinical Cancer Research131762\u20131768. (doi:10.1158\/1078-0432.CCR-06-1812).","DOI":"10.1158\/1078-0432.CCR-06-1812"},{"key":"2026070909024517100_bib13","doi-asserted-by":"crossref","unstructured":"Besse\n B\n \n \n Planchard\n D\n \n \n Veillard\n AS\n \n \n Taillade\n L\n \n \n Khayat\n D\n \n \n Ducourtieux\n M\n \n \n Pignon\n JP\n \n \n Lumbroso\n J\n \n \n Lafontaine\n C\n \n \n Mathiot\n C\n \n \n \n 2012\n Phase 2 study of frontline bortezomib in patients with advanced non-small cell lung cancer. Lung Cancer7678\u201383. (doi:10.1016\/j.lungcan.2011.09.006).","DOI":"10.1016\/j.lungcan.2011.09.006"},{"key":"2026070909024517100_bib14","doi-asserted-by":"crossref","unstructured":"Bonner\n JA\n \n \n Harari\n PM\n \n \n Giralt\n J\n \n \n Cohen\n RB\n \n \n Jones\n CU\n \n \n Sur\n RK\n \n \n Raben\n D\n \n \n Baselga\n J\n \n \n Spencer\n SA\n \n \n Zhu\n J\n \n \n \n 2010\n Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncology1121\u201328. (doi:10.1016\/S1470-2045(09)70311-0).","DOI":"10.1016\/S1470-2045(09)70311-0"},{"key":"2026070909024517100_bib15","doi-asserted-by":"crossref","unstructured":"Bross\n PF\n \n \n Kane\n R\n \n \n Farrell\n AT\n \n \n Abraham\n S\n \n \n Benson\n K\n \n \n Brower\n ME\n \n \n Bradley\n S\n \n \n Gobburu\n JV\n \n \n Goheer\n A\n \n \n Lee\n SL\n \n \n \n 2004\n Approval summary for bortezomib for injection in the treatment of multiple myeloma. Clinical Cancer Research103954\u20133964. (doi:10.1158\/1078-0432.CCR-03-0781).","DOI":"10.1158\/1078-0432.CCR-03-0781"},{"key":"2026070909024517100_bib16","doi-asserted-by":"crossref","unstructured":"Brown\n CJ\n \n \n Lain\n S\n \n \n Verma\n CS\n \n \n Fersht\n AR\n \n \n Lane\n DP\n \n \n 2009\n Awakening guardian angels: drugging the p53 pathway. Nature Reviews. Cancer9862\u2013873. (doi:10.1038\/nrc2763).","DOI":"10.1038\/nrc2763"},{"key":"2026070909024517100_bib17","doi-asserted-by":"crossref","unstructured":"Brownell\n JE\n \n \n Sintchak\n MD\n \n \n Gavin\n JM\n \n \n Liao\n H\n \n \n Bruzzese\n FJ\n \n \n Bump\n NJ\n \n \n Soucy\n TA\n \n \n Milhollen\n MA\n \n \n Yang\n X\n \n \n Burkhardt\n AL\n \n \n \n 2010\n Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ. Molecular Cell37102\u2013111. (doi:10.1016\/j.molcel.2009.12.024).","DOI":"10.1016\/j.molcel.2009.12.024"},{"key":"2026070909024517100_bib18","doi-asserted-by":"crossref","unstructured":"Cavaletti\n G\n \n \n Jakubowiak\n AJ\n \n \n 2010\n Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies. Leukemia & Lymphoma511178\u20131187. (doi:10.3109\/10428194.2010.483303).","DOI":"10.3109\/10428194.2010.483303"},{"key":"2026070909024517100_bib19","doi-asserted-by":"crossref","unstructured":"Chaturvedi\n AK\n \n \n Engels\n EA\n \n \n Anderson\n WF\n \n \n Gillison\n ML\n \n \n 2008\n Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. Journal of Clinical Oncology26612\u2013619. (doi:10.1200\/JCO.2007.14.1713).","DOI":"10.1200\/JCO.2007.14.1713"},{"key":"2026070909024517100_bib20","doi-asserted-by":"crossref","unstructured":"Chaturvedi\n AK\n \n \n Engels\n EA\n \n \n Pfeiffer\n RM\n \n \n Hernandez\n BY\n \n \n Xiao\n W\n \n \n Kim\n E\n \n \n Jiang\n B\n \n \n Goodman\n MT\n \n \n Sibug-Saber\n M\n \n \n Cozen\n W\n \n \n \n 2011\n Human papillomavirus and rising oropharyngeal cancer incidence in the United States. Journal of Clinical Oncology294294\u20134301. (doi:10.1200\/JCO.2011.36.4596).","DOI":"10.1200\/JCO.2011.36.4596"},{"key":"2026070909024517100_bib21","doi-asserted-by":"crossref","unstructured":"Chauhan\n D\n \n \n Catley\n L\n \n \n Li\n G\n \n \n Podar\n K\n \n \n Hideshima\n T\n \n \n Velankar\n M\n \n \n Mitsiades\n C\n \n \n Mitsiades\n N\n \n \n Yasui\n H\n \n \n Letai\n A\n \n \n \n 2005\n A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell8407\u2013419. (doi:10.1016\/j.ccr.2005.10.013).","DOI":"10.1016\/j.ccr.2005.10.013"},{"key":"2026070909024517100_bib22","doi-asserted-by":"crossref","unstructured":"Chauhan\n D\n \n \n Singh\n AV\n \n \n Aujay\n M\n \n \n Kirk\n CJ\n \n \n Bandi\n M\n \n \n Ciccarelli\n B\n \n \n Raje\n N\n \n \n Richardson\n P\n \n \n Anderson\n KC\n \n \n 2010\n A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood1164906\u20134915. (doi:10.1182\/blood-2010-04-276626).","DOI":"10.1182\/blood-2010-04-276626"},{"key":"2026070909024517100_bib23","doi-asserted-by":"crossref","unstructured":"Chauhan\n D\n \n \n Tian\n Z\n \n \n Zhou\n B\n \n \n Kuhn\n D\n \n \n Orlowski\n R\n \n \n Raje\n N\n \n \n Richardson\n P\n \n \n Anderson\n KC\n \n \n 2011\n \n In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clinical Cancer Research175311\u20135321. (doi:10.1158\/1078-0432.CCR-11-0476).","DOI":"10.1158\/1078-0432.CCR-11-0476"},{"key":"2026070909024517100_bib24","doi-asserted-by":"crossref","unstructured":"Chauhan\n D\n \n \n Tian\n Z\n \n \n Nicholson\n B\n \n \n Kumar\n KG\n \n \n Zhou\n B\n \n \n Carrasco\n R\n \n \n McDermott\n JL\n \n \n Leach\n CA\n \n \n Fulcinniti\n M\n \n \n Kodrasov\n MP\n \n \n \n 2012\n A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell22345\u2013358. (doi:10.1016\/j.ccr.2012.08.007).","DOI":"10.1016\/j.ccr.2012.08.007"},{"key":"2026070909024517100_bib25","unstructured":"Chen\n D\n \n \n Dou\n QP\n \n \n 2010\n The ubiquitin\u2013proteasome system as a prospective molecular target for cancer treatment and prevention. Current Protein & Peptide Science11459\u2013470. (doi:10.2174\/138920310791824057)."},{"key":"2026070909024517100_bib26","doi-asserted-by":"crossref","unstructured":"Chen\n KF\n \n \n Yeh\n PY\n \n \n Hsu\n C\n \n \n Hsu\n CH\n \n \n Lu\n YS\n \n \n Hsieh\n HP\n \n \n Chen\n PJ\n \n \n Cheng\n AL\n \n \n 2009\n Bortezomib overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells in part through the inhibition of the phosphatidylinositol 3-kinase\/Akt pathway. Journal of Biological Chemistry28411121\u201311133. (doi:10.1074\/jbc.M806268200).","DOI":"10.1074\/jbc.M806268200"},{"key":"2026070909024517100_bib27","doi-asserted-by":"crossref","unstructured":"Chen\n D\n \n \n Frezza\n M\n \n \n Schmitt\n S\n \n \n Kanwar\n J\n \n \n Dou\n QP\n \n \n 2011\n Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Current Cancer Drug Targets11239\u2013253. (doi:10.2174\/156800911794519752).","DOI":"10.2174\/156800911794519752"},{"key":"2026070909024517100_bib28","doi-asserted-by":"crossref","unstructured":"Chung\n CH\n \n \n Aulino\n J\n \n \n Muldowney\n NJ\n \n \n Hatakeyama\n H\n \n \n Baumann\n J\n \n \n Burkey\n B\n \n \n Netterville\n J\n \n \n Sinard\n R\n \n \n Yarbrough\n WG\n \n \n Cmelak\n AJ\n \n \n \n 2010\n Nuclear factor-\u03baB pathway and response in a phase II trial of bortezomib and docetaxel in patients with recurrent and\/or metastatic head and neck squamous cell carcinoma. Annals of Oncology21864\u2013870. (doi:10.1093\/annonc\/mdp390).","DOI":"10.1093\/annonc\/mdp390"},{"key":"2026070909024517100_bib29","unstructured":"Ciechanover\n A\n \n \n 2005\n Proteolysis: from the lysosome to ubiquitin and the proteasome. Nature Reviews. Molecular Cell Biology679\u201387. (doi:10.1038\/nrm1552)."},{"key":"2026070909024517100_bib30","doi-asserted-by":"crossref","unstructured":"Corso\n A\n \n \n Mangiacavalli\n S\n \n \n Varettoni\n M\n \n \n Pascutto\n C\n \n \n Zappasodi\n P\n \n \n Lazzarino\n M\n \n \n 2010\n Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients. Leukemia Research34471\u2013474. (doi:10.1016\/j.leukres.2009.07.022).","DOI":"10.1016\/j.leukres.2009.07.022"},{"key":"2026070909024517100_bib31","doi-asserted-by":"crossref","unstructured":"Dasmahapatra\n G\n \n \n Lembersky\n D\n \n \n Kramer\n L\n \n \n Fisher\n RI\n \n \n Friedberg\n J\n \n \n Dent\n P\n \n \n Grant\n S\n \n \n 2010\n The pan-HDAC inhibitor vorinostat potentiates the activity of the proteasome inhibitor carfilzomib in human DLBCL cells in vitro and in vivo. Blood1154478\u20134487. (doi:10.1182\/blood-2009-12-257261).","DOI":"10.1182\/blood-2009-12-257261"},{"key":"2026070909024517100_bib32","unstructured":"Dasmahapatra\n G\n \n \n Lembersky\n D\n \n \n Son\n MP\n \n \n Attkisson\n E\n \n \n Dent\n P\n \n \n Fisher\n RI\n \n \n Friedberg\n JW\n \n \n Grant\n S\n \n \n 2011\n Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo. Molecular Cancer Therapeutics101686\u20131697. (doi:10.1158\/1535-7163.MCT-10-1108)."},{"key":"2026070909024517100_bib33","doi-asserted-by":"crossref","unstructured":"Davies\n AM\n \n \n Chansky\n K\n \n \n Lara\n PN\n Jr\n \n \n Gumerlock\n PH\n \n \n Crowley\n J\n \n \n Albain\n KS\n \n \n Vogel\n SJ\n \n \n Gandara\n DR\n \n \n Southwest Oncology G\n \n \n \n 2009\n Bortezomib plus gemcitabine\/carboplatin as first-line treatment of advanced non-small cell lung cancer: a phase II Southwest Oncology Group Study (S0339). Journal of Thoracic Oncology487\u201392. (doi:10.1097\/JTO.0b013e3181915052).","DOI":"10.1097\/JTO.0b013e3181915052"},{"key":"2026070909024517100_bib34","doi-asserted-by":"crossref","unstructured":"Demo\n SD\n \n \n Kirk\n CJ\n \n \n Aujay\n MA\n \n \n Buchholz\n TJ\n \n \n Dajee\n M\n \n \n Ho\n MN\n \n \n Jiang\n J\n \n \n Laidig\n GJ\n \n \n Lewis\n ER\n \n \n Parlati\n F\n \n \n \n 2007\n Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Research676383\u20136391. (doi:10.1158\/0008-5472.CAN-06-4086).","DOI":"10.1158\/0008-5472.CAN-06-4086"},{"key":"2026070909024517100_bib35","doi-asserted-by":"crossref","unstructured":"Dimopoulos\n M\n \n \n Siegel\n DS\n \n \n Lonial\n S\n \n \n Qi\n J\n \n \n Hajek\n R\n \n \n Facon\n T\n \n \n Rosinol\n L\n \n \n Williams\n C\n \n \n Blacklock\n H\n \n \n Goldschmidt\n H\n \n \n \n 2013\n Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncology141129\u20131140. (doi:10.1016\/S1470-2045(13)70398-X).","DOI":"10.1016\/S1470-2045(13)70398-X"},{"key":"2026070909024517100_bib36","doi-asserted-by":"crossref","unstructured":"Ding\n WX\n \n \n Ni\n HM\n \n \n Gao\n W\n \n \n Yoshimori\n T\n \n \n Stolz\n DB\n \n \n Ron\n D\n \n \n Yin\n XM\n \n \n 2007\n Linking of autophagy to ubiquitin\u2013proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. American Journal of Pathology171513\u2013524. (doi:10.2353\/ajpath.2007.070188).","DOI":"10.2353\/ajpath.2007.070188"},{"key":"2026070909024517100_bib37","doi-asserted-by":"crossref","unstructured":"Ding\n WX\n \n \n Ni\n HM\n \n \n Gao\n W\n \n \n Chen\n X\n \n \n Kang\n JH\n \n \n Stolz\n DB\n \n \n Liu\n J\n \n \n Yin\n XM\n \n \n 2009\n Oncogenic transformation confers a selective susceptibility to the combined suppression of the proteasome and autophagy. Molecular Cancer Therapeutics82036\u20132045. (doi:10.1158\/1535-7163.MCT-08-1169).","DOI":"10.1158\/1535-7163.MCT-08-1169"},{"key":"2026070909024517100_bib38","unstructured":"Dorsey\n BD\n \n \n Iqbal\n M\n \n \n Chatterjee\n S\n \n \n Menta\n E\n \n \n Bernardini\n R\n \n \n Bernareggi\n A\n \n \n Cassara\n PG\n \n \n D'Arasmo\n G\n \n \n Ferretti\n E\n \n \n De Munari\n S\n \n \n \n 2008\n Discovery of a potent, selective, and orally active proteasome inhibitor for the treatment of cancer. Journal of Medicinal Chemistry511068\u20131072. (doi:10.1021\/jm7010589)."},{"key":"2026070909024517100_bib39","doi-asserted-by":"crossref","unstructured":"Driscoll\n JJ\n \n \n Woodle\n ES\n \n \n 2012\n Targeting the ubiquitin+proteasome system in solid tumors. Seminars in Hematology49277\u2013283. (doi:10.1053\/j.seminhematol.2012.04.002).","DOI":"10.1053\/j.seminhematol.2012.04.002"},{"key":"2026070909024517100_bib40","doi-asserted-by":"crossref","unstructured":"Dudek\n AZ\n \n \n Lesniewski-Kmak\n K\n \n \n Shehadeh\n NJ\n \n \n Pandey\n ON\n \n \n Franklin\n M\n \n \n Kratzke\n RA\n \n \n Greeno\n EW\n \n \n Kumar\n P\n \n \n 2009\n Phase I study of bortezomib and cetuximab in patients with solid tumours expressing epidermal growth factor receptor. British Journal of Cancer1001379\u20131384. (doi:10.1038\/sj.bjc.6605043).","DOI":"10.1038\/sj.bjc.6605043"},{"key":"2026070909024517100_bib41","doi-asserted-by":"crossref","unstructured":"Fang\n Y\n \n \n Hu\n Y\n \n \n Wu\n P\n \n \n Wang\n B\n \n \n Tian\n Y\n \n \n Xia\n X\n \n \n Zhang\n Q\n \n \n Chen\n T\n \n \n Jiang\n X\n \n \n Ma\n Q\n \n \n \n 2011\n Synergistic efficacy in human ovarian cancer cells by histone deacetylase inhibitor TSA and proteasome inhibitor PS-341. Cancer Investigation29247\u2013252. (doi:10.3109\/07357907.2010.496756).","DOI":"10.3109\/07357907.2010.496756"},{"key":"2026070909024517100_bib42","doi-asserted-by":"crossref","unstructured":"Feling\n RH\n \n \n Buchanan\n GO\n \n \n Mincer\n TJ\n \n \n Kauffman\n CA\n \n \n Jensen\n PR\n \n \n Fenical\n W\n \n \n 2003\n Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. Angewandte Chemie42355\u2013357. (doi:10.1002\/anie.200390115).","DOI":"10.1002\/chin.200319208"},{"key":"2026070909024517100_bib43","doi-asserted-by":"crossref","unstructured":"Fisher\n RI\n \n \n Bernstein\n SH\n \n \n Kahl\n BS\n \n \n Djulbegovic\n B\n \n \n Robertson\n MJ\n \n \n de Vos\n S\n \n \n Epner\n E\n \n \n Krishnan\n A\n \n \n Leonard\n JP\n \n \n Lonial\n S\n \n \n \n 2006\n Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. Journal of Clinical Oncology244867\u20134874. (doi:10.1200\/JCO.2006.07.9665).","DOI":"10.1200\/JCO.2006.07.9665"},{"key":"2026070909024517100_bib44","unstructured":"Fraile\n JM\n \n \n Quesada\n V\n \n \n Rodriguez\n D\n \n \n Freije\n JM\n \n \n Lopez-Otin\n C\n \n \n 2012\n Deubiquitinases in cancer: new functions and therapeutic options. Oncogene312373\u20132388. (doi:10.1038\/onc.2011.443)."},{"key":"2026070909024517100_bib45","doi-asserted-by":"crossref","unstructured":"Frankland-Searby\n S\n \n \n Bhaumik\n SR\n \n \n 2012\n The 26S proteasome complex: an attractive target for cancer therapy. Biochimica et Biophysica Acta182564\u201376. (doi:10.1016\/j.bbcan.2011.10.003).","DOI":"10.1016\/j.bbcan.2011.10.003"},{"key":"2026070909024517100_bib46","doi-asserted-by":"crossref","unstructured":"Fribley\n A\n \n \n Zeng\n Q\n \n \n Wang\n CY\n \n \n 2004\n Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Molecular and Cellular Biology249695\u20139704. (doi:10.1128\/MCB.24.22.9695-9704.2004).","DOI":"10.1128\/MCB.24.22.9695-9704.2004"},{"key":"2026070909024517100_bib47","doi-asserted-by":"crossref","unstructured":"Fribley\n AM\n \n \n Evenchik\n B\n \n \n Zeng\n Q\n \n \n Park\n BK\n \n \n Guan\n JY\n \n \n Zhang\n H\n \n \n Hale\n TJ\n \n \n Soengas\n MS\n \n \n Kaufman\n RJ\n \n \n Wang\n CY\n \n \n 2006\n Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa. Journal of Biological Chemistry28131440\u201331447. (doi:10.1074\/jbc.M604356200).","DOI":"10.1016\/S0021-9258(19)84056-5"},{"key":"2026070909024517100_bib48","doi-asserted-by":"crossref","unstructured":"Gallastegui\n N\n \n \n Groll\n M\n \n \n 2010\n The 26S proteasome: assembly and function of a destructive machine. Trends in Biochemical Sciences35634\u2013642. (doi:10.1016\/j.tibs.2010.05.005).","DOI":"10.1016\/j.tibs.2010.05.005"},{"key":"2026070909024517100_bib49","doi-asserted-by":"crossref","unstructured":"Gatti\n L\n \n \n Benedetti\n V\n \n \n De Cesare\n M\n \n \n Corna\n E\n \n \n Cincinelli\n R\n \n \n Zaffaroni\n N\n \n \n Zunino\n F\n \n \n Perego\n P\n \n \n 2012\n Synergistic interaction between the novel histone deacetylase inhibitor ST2782 and the proteasome inhibitor bortezomib in platinum-sensitive and resistant ovarian carcinoma cells. Journal of Inorganic Biochemistry11394\u2013101. (doi:10.1016\/j.jinorgbio.2012.04.007).","DOI":"10.1016\/j.jinorgbio.2012.04.007"},{"key":"2026070909024517100_bib50","doi-asserted-by":"crossref","unstructured":"Ghosh\n S\n \n \n Baltimore\n D\n \n \n 1990\n Activation in vitro of NF-\u03baB by phosphorylation of its inhibitor I\u03baB. Nature344678\u2013682. (doi:10.1038\/344678a0).","DOI":"10.1038\/344678a0"},{"key":"2026070909024517100_bib51","doi-asserted-by":"crossref","unstructured":"Ghosh\n S\n \n \n Karin\n M\n \n \n 2002\n Missing pieces in the NF-\u03baB puzzle. Cell109 (Suppl) S81\u2013S96. (doi:10.1016\/S0092-8674(02)00703-1).","DOI":"10.1016\/S0092-8674(02)00703-1"},{"key":"2026070909024517100_bib52","doi-asserted-by":"crossref","unstructured":"Gilbert\n J\n \n \n Lee\n JW\n \n \n Argiris\n A\n \n \n Haigentz\n M\n Jr\n \n \n Feldman\n LE\n \n \n Jang\n M\n \n \n Arun\n P\n \n \n Van Waes\n C\n \n \n Forastiere\n AA\n \n \n 2013\n Phase II 2-arm trial of the proteasome inhibitor, PS-341 (bortezomib) in combination with irinotecan or PS-341 alone followed by the addition of irinotecan at time of progression in patients with locally recurrent or metastatic squamous cell carcinoma of the head and neck (E1304): a trial of the Eastern Cooperative Oncology Group. Head & Neck35942\u2013948. (doi:10.1002\/hed.23046).","DOI":"10.1002\/hed.23046"},{"key":"2026070909024517100_bib53","doi-asserted-by":"crossref","unstructured":"Groll\n M\n \n \n Ditzel\n L\n \n \n Lowe\n J\n \n \n Stock\n D\n \n \n Bochtler\n M\n \n \n Bartunik\n HD\n \n \n Huber\n R\n \n \n 1997\n Structure of 20S proteasome from yeast at 2.4\u00c5 resolution. Nature386463\u2013471. (doi:10.1038\/386463a0).","DOI":"10.2210\/pdb1ryp\/pdb"},{"key":"2026070909024517100_bib54","doi-asserted-by":"crossref","unstructured":"Herndon\n TM\n \n \n Deisseroth\n A\n \n \n Kaminskas\n E\n \n \n Kane\n RC\n \n \n Koti\n KM\n \n \n Rothmann\n MD\n \n \n Habtemariam\n B\n \n \n Bullock\n J\n \n \n Bray\n JD\n \n \n Hawes\n J\n \n \n \n 2013\n U.S. Food and Drug Administration approval: carfilzomib for the treatment of multiple myeloma. Clinical Cancer Research194559\u20134563. (doi:10.1158\/1078-0432.CCR-13-0755).","DOI":"10.1158\/1078-0432.CCR-13-0755"},{"key":"2026070909024517100_bib55","doi-asserted-by":"crossref","unstructured":"Hideshima\n T\n \n \n Richardson\n PG\n \n \n Anderson\n KC\n \n \n 2011\n Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma. Molecular Cancer Therapeutics102034\u20132042. (doi:10.1158\/1535-7163.MCT-11-0433).","DOI":"10.1158\/1535-7163.MCT-11-0433"},{"key":"2026070909024517100_bib56","doi-asserted-by":"crossref","unstructured":"Hoang\n T\n \n \n Campbell\n TC\n \n \n Zhang\n C\n \n \n Kim\n K\n \n \n Kolesar\n JM\n \n \n Oettel\n KR\n \n \n Blank\n JH\n \n \n Robinson\n EG\n \n \n Ahuja\n HG\n \n \n Kirschling\n RJ\n \n \n \n 2013\n Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study. Investigational New Drugs32195\u2013199. (doi:10.1007\/s10637-013-9980-5).","DOI":"10.1007\/s10637-013-9980-5"},{"key":"2026070909024517100_bib57","doi-asserted-by":"crossref","unstructured":"Hui\n B\n \n \n Shi\n YH\n \n \n Ding\n ZB\n \n \n Zhou\n J\n \n \n Gu\n CY\n \n \n Peng\n YF\n \n \n Yang\n H\n \n \n Liu\n WR\n \n \n Shi\n GM\n \n \n Fan\n J\n \n \n 2012\n Proteasome inhibitor interacts synergistically with autophagy inhibitor to suppress proliferation and induce apoptosis in hepatocellular carcinoma. Cancer1185560\u20135571. (doi:10.1002\/cncr.27586).","DOI":"10.1002\/cncr.27586"},{"key":"2026070909024517100_bib58","doi-asserted-by":"crossref","unstructured":"Irvin\n WJ\n Jr\n \n \n Orlowski\n RZ\n \n \n Chiu\n WK\n \n \n Carey\n LA\n \n \n Collichio\n FA\n \n \n Bernard\n PS\n \n \n Stijleman\n IJ\n \n \n Perou\n C\n \n \n Ivanova\n A\n \n \n Dees\n EC\n \n \n 2010\n Phase II study of bortezomib and pegylated liposomal doxorubicin in the treatment of metastatic breast cancer. Clinical Breast Cancer10465\u2013470. (doi:10.3816\/CBC.2010.n.061).","DOI":"10.3816\/CBC.2010.n.061"},{"key":"2026070909024517100_bib59","unstructured":"Kale\n AJ\n \n \n Moore\n BS\n \n \n 2012\n Molecular mechanisms of acquired proteasome inhibitor resistance. Journal of Medicinal Chemistry5510317\u201310327. (doi:10.1021\/jm300434z)."},{"key":"2026070909024517100_bib60","doi-asserted-by":"crossref","unstructured":"Kane\n RC\n \n \n Bross\n PF\n \n \n Farrell\n AT\n \n \n Pazdur\n R\n \n \n 2003\n Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist8508\u2013513. (doi:10.1634\/theoncologist.8-6-508).","DOI":"10.1634\/theoncologist.8-6-508"},{"key":"2026070909024517100_bib61","doi-asserted-by":"crossref","unstructured":"Kane\n RC\n \n \n Dagher\n R\n \n \n Farrell\n A\n \n \n Ko\n CW\n \n \n Sridhara\n R\n \n \n Justice\n R\n \n \n Pazdur\n R\n \n \n 2007\n Bortezomib for the treatment of mantle cell lymphoma. Clinical Cancer Research135291\u20135294. (doi:10.1158\/1078-0432.CCR-07-0871).","DOI":"10.1158\/1078-0432.CCR-07-0871"},{"key":"2026070909024517100_bib62","doi-asserted-by":"crossref","unstructured":"Kim\n J\n \n \n Guan\n J\n \n \n Chang\n I\n \n \n Chen\n X\n \n \n Han\n D\n \n \n Wang\n CY\n \n \n 2010\n PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells. Molecular Cancer Therapeutics91977\u20131984. (doi:10.1158\/1535-7163.MCT-10-0141).","DOI":"10.1158\/1535-7163.MCT-10-0141"},{"key":"2026070909024517100_bib63","unstructured":"Kim\n GP\n \n \n Mahoney\n MR\n \n \n Szydlo\n D\n \n \n Mok\n TS\n \n \n Marshke\n R\n \n \n Holen\n K\n \n \n Picus\n J\n \n \n Boyer\n M\n \n \n Pitot\n HC\n \n \n Rubin\n J\n \n \n \n 2012\n An international, multicenter phase II trial of bortezomib in patients with hepatocellular carcinoma. Investigational New Drugs30387\u2013394. (doi:10.1007\/s10637-010-9532-1)."},{"key":"2026070909024517100_bib64","doi-asserted-by":"crossref","unstructured":"Kozuch\n PS\n \n \n Rocha-Lima\n CM\n \n \n Dragovich\n T\n \n \n Hochster\n H\n \n \n O'Neil\n BH\n \n \n Atiq\n OT\n \n \n Pipas\n JM\n \n \n Ryan\n DP\n \n \n Lenz\n HJ\n \n \n 2008\n Bortezomib with or without irinotecan in relapsed or refractory colorectal cancer: results from a randomized phase II study. Journal of Clinical Oncology262320\u20132326. (doi:10.1200\/JCO.2007.14.0152).","DOI":"10.1200\/JCO.2007.14.0152"},{"key":"2026070909024517100_bib65","doi-asserted-by":"crossref","unstructured":"Kraft\n AS\n \n \n Garrett-Mayer\n E\n \n \n Wahlquist\n AE\n \n \n Golshayan\n A\n \n \n Chen\n CS\n \n \n Butler\n W\n \n \n Bearden\n J\n \n \n Lilly\n M\n \n \n 2011\n Combination therapy of recurrent prostate cancer with the proteasome inhibitor bortezomib plus hormone blockade. Cancer Biology & Therapy12119\u2013124. (doi:10.4161\/cbt.12.2.15723).","DOI":"10.4161\/cbt.12.2.15723"},{"key":"2026070909024517100_bib66","doi-asserted-by":"crossref","unstructured":"Kubicek\n GJ\n \n \n Axelrod\n RS\n \n \n Machtay\n M\n \n \n Ahn\n PH\n \n \n Anne\n PR\n \n \n Fogh\n S\n \n \n Cognetti\n D\n \n \n Myers\n TJ\n \n \n Curran\n WJ\n Jr\n \n \n Dicker\n AP\n \n \n 2012\n Phase I trial using the proteasome inhibitor bortezomib and concurrent chemoradiotherapy for head-and-neck malignancies. International Journal of Radiation Oncology, Biology, Physics831192\u20131197. (doi:10.1016\/j.ijrobp.2011.09.023).","DOI":"10.1016\/j.ijrobp.2011.09.023"},{"key":"2026070909024517100_bib67","doi-asserted-by":"crossref","unstructured":"Kuhn\n DJ\n \n \n Chen\n Q\n \n \n Voorhees\n PM\n \n \n Strader\n JS\n \n \n Shenk\n KD\n \n \n Sun\n CM\n \n \n Demo\n SD\n \n \n Bennett\n MK\n \n \n van Leeuwen\n FW\n \n \n Chanan-Khan\n AA\n \n \n \n 2007\n Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin\u2013proteasome pathway, against preclinical models of multiple myeloma. Blood1103281\u20133290. (doi:10.1182\/blood-2007-01-065888).","DOI":"10.1182\/blood-2007-01-065888"},{"key":"2026070909024517100_bib68","doi-asserted-by":"crossref","unstructured":"Kupperman\n E\n \n \n Lee\n EC\n \n \n Cao\n Y\n \n \n Bannerman\n B\n \n \n Fitzgerald\n M\n \n \n Berger\n A\n \n \n Yu\n J\n \n \n Yang\n Y\n \n \n Hales\n P\n \n \n Bruzzese\n F\n \n \n \n 2010\n Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Research701970\u20131980. (doi:10.1158\/0008-5472.CAN-09-2766).","DOI":"10.1158\/0008-5472.CAN-09-2766"},{"key":"2026070909024517100_bib69","doi-asserted-by":"crossref","unstructured":"Lara\n PN\n Jr\n \n \n Longmate\n J\n \n \n Reckamp\n K\n \n \n Gitlitz\n B\n \n \n Argiris\n A\n \n \n Ramalingam\n S\n \n \n Belani\n CP\n \n \n Mack\n PC\n \n \n Lau\n DH\n \n \n Koczywas\n M\n \n \n \n 2011\n Randomized phase II trial of concurrent versus sequential bortezomib plus docetaxel in advanced non-small-cell lung cancer: a California cancer consortium trial. Clinical Lung Cancer1233\u201337. (doi:10.3816\/CLC.2011.n.004).","DOI":"10.3816\/CLC.2011.n.004"},{"key":"2026070909024517100_bib70","doi-asserted-by":"crossref","unstructured":"Li\n C\n \n \n Johnson\n DE\n \n \n 2012\n Bortezomib induces autophagy in head and neck squamous cell carcinoma cells via JNK activation. Cancer Letters314102\u2013107. (doi:10.1016\/j.canlet.2011.09.020).","DOI":"10.1016\/j.canlet.2011.09.020"},{"key":"2026070909024517100_bib71","doi-asserted-by":"crossref","unstructured":"Li\n C\n \n \n Li\n R\n \n \n Grandis\n JR\n \n \n Johnson\n DE\n \n \n 2008\n Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells. Molecular Cancer Therapeutics71647\u20131655. (doi:10.1158\/1535-7163.MCT-07-2444).","DOI":"10.1158\/1535-7163.MCT-07-2444"},{"key":"2026070909024517100_bib72","doi-asserted-by":"crossref","unstructured":"Li\n C\n \n \n Zang\n Y\n \n \n Sen\n M\n \n \n Leeman-Neill\n RJ\n \n \n Man\n DS\n \n \n Grandis\n JR\n \n \n Johnson\n DE\n \n \n 2009\n Bortezomib up-regulates activated signal transducer and activator of transcription-3 and synergizes with inhibitors of signal transducer and activator of transcription-3 to promote head and neck squamous cell carcinoma cell death. Molecular Cancer Therapeutics82211\u20132220. (doi:10.1158\/1535-7163.MCT-09-0327).","DOI":"10.1158\/1535-7163.MCT-09-0327"},{"key":"2026070909024517100_bib73","doi-asserted-by":"crossref","unstructured":"Li\n T\n \n \n Ho\n L\n \n \n Piperdi\n B\n \n \n Elrafei\n T\n \n \n Camacho\n FJ\n \n \n Rigas\n JR\n \n \n Perez-Soler\n R\n \n \n Gucalp\n R\n \n \n 2010\n Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade) in chemotherapy-naive patients with advanced stage non-small cell lung cancer (NSCLC). Lung Cancer6889\u201393. (doi:10.1016\/j.lungcan.2009.05.009).","DOI":"10.1016\/j.lungcan.2009.05.009"},{"key":"2026070909024517100_bib74","doi-asserted-by":"crossref","unstructured":"Lin\n Z\n \n \n Bazzaro\n M\n \n \n Wang\n MC\n \n \n Chan\n KC\n \n \n Peng\n S\n \n \n Roden\n RB\n \n \n 2009\n Combination of proteasome and HDAC inhibitors for uterine cervical cancer treatment. Clinical Cancer Research15570\u2013577. (doi:10.1158\/1078-0432.CCR-08-1813).","DOI":"10.1158\/1078-0432.CCR-08-1813"},{"key":"2026070909024517100_bib75","doi-asserted-by":"crossref","unstructured":"Linenberger\n ML\n \n \n Hong\n T\n \n \n Flowers\n D\n \n \n Sievers\n EL\n \n \n Gooley\n TA\n \n \n Bennett\n JM\n \n \n Berger\n MS\n \n \n Leopold\n LH\n \n \n Appelbaum\n FR\n \n \n Bernstein\n ID\n \n \n 2001\n Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin. Blood98988\u2013994. (doi:10.1182\/blood.V98.4.988).","DOI":"10.1182\/blood.V98.4.988"},{"key":"2026070909024517100_bib76","doi-asserted-by":"crossref","unstructured":"Liu\n X\n \n \n Yue\n P\n \n \n Chen\n S\n \n \n Hu\n L\n \n \n Lonial\n S\n \n \n Khuri\n FR\n \n \n Sun\n SY\n \n \n 2007\n The proteasome inhibitor PS-341 (bortezomib) up-regulates DR5 expression leading to induction of apoptosis and enhancement of TRAIL-induced apoptosis despite up-regulation of c-FLIP and survivin expression in human NSCLC cells. Cancer Research674981\u20134988. (doi:10.1158\/0008-5472.CAN-06-4274).","DOI":"10.1158\/0008-5472.CAN-06-4274"},{"key":"2026070909024517100_bib77","doi-asserted-by":"crossref","unstructured":"Liu\n S\n \n \n Liu\n Z\n \n \n Xie\n Z\n \n \n Pang\n J\n \n \n Yu\n J\n \n \n Lehmann\n E\n \n \n Huynh\n L\n \n \n Vukosavljevic\n T\n \n \n Takeki\n M\n \n \n Klisovic\n RB\n \n \n \n 2008\n Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1\/NF-\u03baB-dependent DNA methyltransferase activity in acute myeloid leukemia. Blood1112364\u20132373. (doi:10.1182\/blood-2007-08-110171).","DOI":"10.1182\/blood-2007-08-110171"},{"key":"2026070909024517100_bib78","doi-asserted-by":"crossref","unstructured":"Lonial\n S\n \n \n Waller\n EK\n \n \n Richardson\n PG\n \n \n Jagannath\n S\n \n \n Orlowski\n RZ\n \n \n Giver\n CR\n \n \n Jaye\n DL\n \n \n Francis\n D\n \n \n Giusti\n S\n \n \n Torre\n C\n \n \n \n 2005\n Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. Blood1063777\u20133784. (doi:10.1182\/blood-2005-03-1173).","DOI":"10.1182\/blood-2005-03-1173"},{"key":"2026070909024517100_bib79","doi-asserted-by":"crossref","unstructured":"Macherla\n VR\n \n \n Mitchell\n SS\n \n \n Manam\n RR\n \n \n Reed\n KA\n \n \n Chao\n TH\n \n \n Nicholson\n B\n \n \n Deyanat-Yazdi\n G\n \n \n Mai\n B\n \n \n Jensen\n PR\n \n \n Fenical\n WF\n \n \n \n 2005\n Structure\u2013activity relationship studies of salinosporamide A (NPI-0052), a novel marine derived proteasome inhibitor. Journal of Medicinal Chemistry483684\u20133687. (doi:10.1021\/jm048995+).","DOI":"10.1021\/jm048995+"},{"key":"2026070909024517100_bib80","doi-asserted-by":"crossref","unstructured":"Mackay\n H\n \n \n Hedley\n D\n \n \n Major\n P\n \n \n Townsley\n C\n \n \n Mackenzie\n M\n \n \n Vincent\n M\n \n \n Degendorfer\n P\n \n \n Tsao\n MS\n \n \n Nicklee\n T\n \n \n Birle\n D\n \n \n \n 2005\n A phase II trial with pharmacodynamic endpoints of the proteasome inhibitor bortezomib in patients with metastatic colorectal cancer. Clinical Cancer Research115526\u20135533. (doi:10.1158\/1078-0432.CCR-05-0081).","DOI":"10.1158\/1078-0432.CCR-05-0081"},{"key":"2026070909024517100_bib81","doi-asserted-by":"crossref","unstructured":"Markovic\n SN\n \n \n Geyer\n SM\n \n \n Dawkins\n F\n \n \n Sharfman\n W\n \n \n Albertini\n M\n \n \n Maples\n W\n \n \n Fracasso\n PM\n \n \n Fitch\n T\n \n \n Lorusso\n P\n \n \n Adjei\n AA\n \n \n \n 2005\n A phase II study of bortezomib in the treatment of metastatic malignant melanoma. Cancer1032584\u20132589. (doi:10.1002\/cncr.21108).","DOI":"10.1002\/cncr.21108"},{"key":"2026070909024517100_bib82","doi-asserted-by":"crossref","unstructured":"Merlet\n J\n \n \n Burger\n J\n \n \n Gomes\n JE\n \n \n Pintard\n L\n \n \n 2009\n Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization. Cellular and Molecular Life Sciences 661924\u20131938. (doi:10.1007\/s00018-009-8712-7).","DOI":"10.1007\/s00018-009-8712-7"},{"key":"2026070909024517100_bib83","doi-asserted-by":"crossref","unstructured":"Milhollen\n MA\n \n \n Narayanan\n U\n \n \n Soucy\n TA\n \n \n Veiby\n PO\n \n \n Smith\n PG\n \n \n Amidon\n B\n \n \n 2011\n Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Cancer Research713042\u20133051. (doi:10.1158\/0008-5472.CAN-10-2122).","DOI":"10.1158\/0008-5472.CAN-10-2122"},{"key":"2026070909024517100_bib84","doi-asserted-by":"crossref","unstructured":"Miller\n CP\n \n \n Ban\n K\n \n \n Dujka\n ME\n \n \n McConkey\n DJ\n \n \n Munsell\n M\n \n \n Palladino\n M\n \n \n Chandra\n J\n \n \n 2007\n NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. Blood110267\u2013277. (doi:10.1182\/blood-2006-03-013128).","DOI":"10.1182\/blood-2006-03-013128"},{"key":"2026070909024517100_bib85","unstructured":"Miyashita\n T\n \n \n Reed\n JC\n \n \n 1995\n Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell80293\u2013299. (doi:10.1016\/0092-8674(95)90513-8)."},{"key":"2026070909024517100_bib86","doi-asserted-by":"crossref","unstructured":"Morris\n MJ\n \n \n Kelly\n WK\n \n \n Slovin\n S\n \n \n Ryan\n C\n \n \n Eicher\n C\n \n \n Heller\n G\n \n \n Scher\n HI\n \n \n 2007\n A phase II trial of bortezomib and prednisone for castration resistant metastatic prostate cancer. Journal of Urology1782378\u20132383.(discussion 2383\u20132384) (doi:10.1016\/j.juro.2007.08.015).","DOI":"10.1016\/j.juro.2007.08.015"},{"key":"2026070909024517100_bib87","doi-asserted-by":"crossref","unstructured":"Nasman\n A\n \n \n Attner\n P\n \n \n Hammarstedt\n L\n \n \n Du\n J\n \n \n Eriksson\n M\n \n \n Giraud\n G\n \n \n Ahrlund-Richter\n S\n \n \n Marklund\n L\n \n \n Romanitan\n M\n \n \n Lindquist\n D\n \n \n \n 2009\n Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma?\n International Journal of Cancer\n 125\n 362\u2013366. (doi:10.1002\/ijc.24339).","DOI":"10.1002\/ijc.24339"},{"key":"2026070909024517100_bib88","unstructured":"Nawrocki\n ST\n \n \n Bruns\n CJ\n \n \n Harbison\n MT\n \n \n Bold\n RJ\n \n \n Gotsch\n BS\n \n \n Abbruzzese\n JL\n \n \n Elliott\n P\n \n \n Adams\n J\n \n \n McConkey\n DJ\n \n \n 2002\n Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in orthotopic human pancreatic tumor xenografts. Molecular Cancer Therapeutics11243\u20131253."},{"key":"2026070909024517100_bib89","doi-asserted-by":"crossref","unstructured":"Nikrad\n M\n \n \n Johnson\n T\n \n \n Puthalalath\n H\n \n \n Coultas\n L\n \n \n Adams\n J\n \n \n Kraft\n AS\n \n \n 2005\n The proteasome inhibitor bortezomib sensitizes cells to killing by death receptor ligand TRAIL via BH3-only proteins Bik and Bim. Molecular Cancer Therapeutics4443\u2013449.","DOI":"10.1158\/1535-7163.MCT-04-0260"},{"key":"2026070909024517100_bib90","doi-asserted-by":"crossref","unstructured":"O'Connor\n OA\n \n \n Wright\n J\n \n \n Moskowitz\n C\n \n \n Muzzy\n J\n \n \n MacGregor-Cortelli\n B\n \n \n Stubblefield\n M\n \n \n Straus\n D\n \n \n Portlock\n C\n \n \n Hamlin\n P\n \n \n Choi\n E\n \n \n \n 2005\n Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. Journal of Clinical Oncology23676\u2013684. (doi:10.1200\/JCO.2005.02.050).","DOI":"10.1200\/JCO.2005.02.050"},{"key":"2026070909024517100_bib91","doi-asserted-by":"crossref","unstructured":"O'Connor\n OA\n \n \n Stewart\n AK\n \n \n Vallone\n M\n \n \n Molineaux\n CJ\n \n \n Kunkel\n LA\n \n \n Gerecitano\n JF\n \n \n Orlowski\n RZ\n \n \n 2009\n A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clinical Cancer Research157085\u20137091. (doi:10.1158\/1078-0432.CCR-09-0822).","DOI":"10.1158\/1078-0432.CCR-09-0822"},{"key":"2026070909024517100_bib92","doi-asserted-by":"crossref","unstructured":"Oda\n E\n \n \n Ohki\n R\n \n \n Murasawa\n H\n \n \n Nemoto\n J\n \n \n Shibue\n T\n \n \n Yamashita\n T\n \n \n Tokino\n T\n \n \n Taniguchi\n T\n \n \n Tanaka\n N\n \n \n 2000\n Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science2881053\u20131058. (doi:10.1126\/science.288.5468.1053).","DOI":"10.1126\/science.288.5468.1053"},{"key":"2026070909024517100_bib93","doi-asserted-by":"crossref","unstructured":"Opferman\n JT\n \n \n 2006\n Unraveling MCL-1 degradation. Cell Death and Differentiation131260\u20131262. (doi:10.1038\/sj.cdd.4401978).","DOI":"10.1038\/sj.cdd.4401978"},{"key":"2026070909024517100_bib94","doi-asserted-by":"crossref","unstructured":"Orlowski\n M\n \n \n Wilk\n S\n \n \n 2000\n Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complex. Archives of Biochemistry and Biophysics3831\u201316. (doi:10.1006\/abbi.2000.2036).","DOI":"10.1006\/abbi.2000.2036"},{"key":"2026070909024517100_bib95","doi-asserted-by":"crossref","unstructured":"Orlowski\n RZ\n \n \n Nagler\n A\n \n \n Sonneveld\n P\n \n \n Blade\n J\n \n \n Hajek\n R\n \n \n Spencer\n A\n \n \n San Miguel\n J\n \n \n Robak\n T\n \n \n Dmoszynska\n A\n \n \n Horvath\n N\n \n \n \n 2007\n 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. Journal of Clinical Oncology253892\u20133901. (doi:10.1200\/JCO.2006.10.5460).","DOI":"10.1200\/JCO.2006.10.5460"},{"key":"2026070909024517100_bib96","doi-asserted-by":"crossref","unstructured":"Parma\n G\n \n \n Mancari\n R\n \n \n Del Conte\n G\n \n \n Scambia\n G\n \n \n Gadducci\n A\n \n \n Hess\n D\n \n \n Katsaros\n D\n \n \n Sessa\n C\n \n \n Rinaldi\n A\n \n \n Bertoni\n F\n \n \n \n 2012\n An open-label phase 2 study of twice-weekly bortezomib and intermittent pegylated liposomal doxorubicin in patients with ovarian cancer failing platinum-containing regimens. International Journal of Gynecological Cancer22792\u2013800. (doi:10.1097\/IGC.0b013e318251051a).","DOI":"10.1097\/IGC.0b013e318251051a"},{"key":"2026070909024517100_bib97","doi-asserted-by":"crossref","unstructured":"Pei\n XY\n \n \n Dai\n Y\n \n \n Grant\n S\n \n \n 2004\n Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors. Clinical Cancer Research103839\u20133852. (doi:10.1158\/1078-0432.CCR-03-0561).","DOI":"10.1158\/1078-0432.CCR-03-0561"},{"key":"2026070909024517100_bib98","doi-asserted-by":"crossref","unstructured":"Perez-Galan\n P\n \n \n Roue\n G\n \n \n Villamor\n N\n \n \n Campo\n E\n \n \n Colomer\n D\n \n \n 2007\n The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak. Blood1094441\u20134449. (doi:10.1182\/blood-2006-07-034173).","DOI":"10.1182\/blood-2006-07-034173"},{"key":"2026070909024517100_bib99","doi-asserted-by":"crossref","unstructured":"Perez-Galan\n P\n \n \n Roue\n G\n \n \n Lopez-Guerra\n M\n \n \n Nguyen\n M\n \n \n Villamor\n N\n \n \n Montserrat\n E\n \n \n Shore\n GC\n \n \n Campo\n E\n \n \n Colomer\n D\n \n \n 2008\n BCL-2 phosphorylation modulates sensitivity to the BH3 mimetic GX15-070 (Obatoclax) and reduces its synergistic interaction with bortezomib in chronic lymphocytic leukemia cells. Leukemia221712\u20131720. (doi:10.1038\/leu.2008.175).","DOI":"10.1038\/leu.2008.175"},{"key":"2026070909024517100_bib100","doi-asserted-by":"crossref","unstructured":"Petrocca\n F\n \n \n Altschuler\n G\n \n \n Tan\n SM\n \n \n Mendillo\n ML\n \n \n Yan\n H\n \n \n Jerry\n DJ\n \n \n Kung\n AL\n \n \n Hide\n W\n \n \n Ince\n TA\n \n \n Lieberman\n J\n \n \n 2013\n A genome-wide siRNA screen identifies proteasome addiction as a vulnerability of basal-like triple-negative breast cancer cells. Cancer Cell24182\u2013196. (doi:10.1016\/j.ccr.2013.07.008).","DOI":"10.1016\/j.ccr.2013.07.008"},{"key":"2026070909024517100_bib101","doi-asserted-by":"crossref","unstructured":"Piperdi\n B\n \n \n Walsh\n WV\n \n \n Bradley\n K\n \n \n Zhou\n Z\n \n \n Bathini\n V\n \n \n Hanrahan-Boshes\n M\n \n \n Hutchinson\n L\n \n \n Perez-Soler\n R\n \n \n 2012\n Phase-I\/II study of bortezomib in combination with carboplatin and bevacizumab as first-line therapy in patients with advanced non-small-cell lung cancer. Journal of Thoracic Oncology71032\u20131040. (doi:10.1097\/JTO.0b013e31824de2fa).","DOI":"10.1097\/JTO.0b013e31824de2fa"},{"key":"2026070909024517100_bib102","doi-asserted-by":"crossref","unstructured":"Pitts\n TM\n \n \n Morrow\n M\n \n \n Kaufman\n SA\n \n \n Tentler\n JJ\n \n \n Eckhardt\n SG\n \n \n 2009\n Vorinostat and bortezomib exert synergistic antiproliferative and proapoptotic effects in colon cancer cell models. Molecular Cancer Therapeutics8342\u2013349. (doi:10.1158\/1535-7163.MCT-08-0534).","DOI":"10.1158\/1535-7163.MCT-08-0534"},{"key":"2026070909024517100_bib103","doi-asserted-by":"crossref","unstructured":"Piva\n R\n \n \n Ruggeri\n B\n \n \n Williams\n M\n \n \n Costa\n G\n \n \n Tamagno\n I\n \n \n Ferrero\n D\n \n \n Giai\n V\n \n \n Coscia\n M\n \n \n Peola\n S\n \n \n Massaia\n M\n \n \n \n 2008\n CEP-18770: a novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood1112765\u20132775. (doi:10.1182\/blood-2007-07-100651).","DOI":"10.1182\/blood-2007-07-100651"},{"key":"2026070909024517100_bib104","doi-asserted-by":"crossref","unstructured":"Poeta\n ML\n \n \n Manola\n J\n \n \n Goldwasser\n MA\n \n \n Forastiere\n A\n \n \n Benoit\n N\n \n \n Califano\n JA\n \n \n Ridge\n JA\n \n \n Goodwin\n J\n \n \n Kenady\n D\n \n \n Saunders\n J\n \n \n \n 2007\n TP53 mutations and survival in squamous-cell carcinoma of the head and neck. New England Journal of Medicine3572552\u20132561. (doi:10.1056\/NEJMoa073770).","DOI":"10.1056\/NEJMoa073770"},{"key":"2026070909024517100_bib105","doi-asserted-by":"crossref","unstructured":"Popat\n R\n \n \n Oakervee\n H\n \n \n Williams\n C\n \n \n Cook\n M\n \n \n Craddock\n C\n \n \n Basu\n S\n \n \n Singer\n C\n \n \n Harding\n S\n \n \n Foot\n N\n \n \n Hallam\n S\n \n \n \n 2009\n Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma. British Journal of Haematology144887\u2013894. (doi:10.1111\/j.1365-2141.2008.07572.x).","DOI":"10.1111\/j.1365-2141.2008.07572.x"},{"key":"2026070909024517100_bib106","doi-asserted-by":"crossref","unstructured":"Pugh\n TJ\n \n \n Chen\n C\n \n \n Rabinovitch\n R\n \n \n Eckhardt\n SG\n \n \n Rusthoven\n KE\n \n \n Swing\n R\n \n \n Raben\n D\n \n \n 2010\n Phase I trial of bortezomib and concurrent external beam radiation in patients with advanced solid malignancies. International Journal of Radiation Oncology, Biology, Physics78521\u2013526. (doi:10.1016\/j.ijrobp.2009.07.1715).","DOI":"10.1016\/j.ijrobp.2009.07.1715"},{"key":"2026070909024517100_bib107","doi-asserted-by":"crossref","unstructured":"Qin\n JZ\n \n \n Ziffra\n J\n \n \n Stennett\n L\n \n \n Bodner\n B\n \n \n Bonish\n BK\n \n \n Chaturvedi\n V\n \n \n Bennett\n F\n \n \n Pollock\n PM\n \n \n Trent\n JM\n \n \n Hendrix\n MJ\n \n \n \n 2005\n Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Research656282\u20136293. (doi:10.1158\/0008-5472.CAN-05-0676).","DOI":"10.1158\/0008-5472.CAN-05-0676"},{"key":"2026070909024517100_bib108","doi-asserted-by":"crossref","unstructured":"Ramalingam\n SS\n \n \n Davies\n AM\n \n \n Longmate\n J\n \n \n Edelman\n MJ\n \n \n Lara\n PN\n Jr\n \n \n Vokes\n EE\n \n \n Villalona-Calero\n M\n \n \n Gitlitz\n B\n \n \n Reckamp\n K\n \n \n Salgia\n R\n \n \n \n 2011\n Bortezomib for patients with advanced-stage bronchioloalveolar carcinoma: a California Cancer Consortium Phase II study (NCI 7003). Journal of Thoracic Oncology61741\u20131745. (doi:10.1097\/JTO.0b013e318225924c).","DOI":"10.1097\/JTO.0b013e318225924c"},{"key":"2026070909024517100_bib109","doi-asserted-by":"crossref","unstructured":"Reece\n DE\n \n \n Rodriguez\n GP\n \n \n Chen\n C\n \n \n Trudel\n S\n \n \n Kukreti\n V\n \n \n Mikhael\n J\n \n \n Pantoja\n M\n \n \n Xu\n W\n \n \n Stewart\n AK\n \n \n 2008\n Phase I\u2013II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma. Journal of Clinical Oncology264777\u20134783. (doi:10.1200\/JCO.2007.14.2372).","DOI":"10.1200\/JCO.2007.14.2372"},{"key":"2026070909024517100_bib110","doi-asserted-by":"crossref","unstructured":"Richardson\n PG\n \n \n Barlogie\n B\n \n \n Berenson\n J\n \n \n Singhal\n S\n \n \n Jagannath\n S\n \n \n Irwin\n D\n \n \n Rajkumar\n SV\n \n \n Srkalovic\n G\n \n \n Alsina\n M\n \n \n Alexanian\n R\n \n \n \n 2003\n A phase 2 study of bortezomib in relapsed, refractory myeloma. New England Journal of Medicine3482609\u20132617. (doi:10.1056\/NEJMoa030288).","DOI":"10.1056\/NEJMoa030288"},{"key":"2026070909024517100_bib111","unstructured":"Richardson\n PG\n \n \n Sonneveld\n P\n \n \n Schuster\n MW\n \n \n Irwin\n D\n \n \n Stadtmauer\n EA\n \n \n Facon\n T\n \n \n Harousseau\n JL\n \n \n Ben-Yehuda\n D\n \n \n Lonial\n S\n \n \n Goldschmidt\n H\n \n \n \n 2005\n Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. New England Journal of Medicine3522487\u20132498. (doi:10.1056\/NEJMoa043445)."},{"key":"2026070909024517100_bib112","doi-asserted-by":"crossref","unstructured":"Richardson\n PG\n \n \n Briemberg\n H\n \n \n Jagannath\n S\n \n \n Wen\n PY\n \n \n Barlogie\n B\n \n \n Berenson\n J\n \n \n Singhal\n S\n \n \n Siegel\n DS\n \n \n Irwin\n D\n \n \n Schuster\n M\n \n \n \n 2006\n Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. Journal of Clinical Oncology243113\u20133120. (doi:10.1200\/JCO.2005.04.7779).","DOI":"10.1200\/JCO.2005.04.7779"},{"key":"2026070909024517100_bib113","doi-asserted-by":"crossref","unstructured":"Richardson\n PG\n \n \n Schlossman\n RL\n \n \n Alsina\n M\n \n \n Weber\n DM\n \n \n Coutre\n SE\n \n \n Gasparetto\n C\n \n \n Mukhopadhyay\n S\n \n \n Ondovik\n MS\n \n \n Khan\n M\n \n \n Paley\n CS\n \n \n \n 2013\n PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood1222331\u20132337. (doi:10.1182\/blood-2013-01-481325).","DOI":"10.1182\/blood-2013-01-481325"},{"key":"2026070909024517100_bib114","doi-asserted-by":"crossref","unstructured":"Saha\n MN\n \n \n Qiu\n L\n \n \n Chang\n H\n \n \n 2013\n Targeting p53 by small molecules in hematological malignancies. Journal of Hematology & Oncology623. (doi:10.1186\/1756-8722-6-23).","DOI":"10.1186\/1756-8722-6-23"},{"key":"2026070909024517100_bib115","doi-asserted-by":"crossref","unstructured":"Scheffner\n M\n \n \n Huibregtse\n JM\n \n \n Vierstra\n RD\n \n \n Howley\n PM\n \n \n 1993\n The HPV-16 E6 and E6-AP complex functions as a ubiquitin\u2013protein ligase in the ubiquitination of p53. Cell75495\u2013505. (doi:10.1016\/0092-8674(93)90384-3).","DOI":"10.1016\/0092-8674(93)90384-3"},{"key":"2026070909024517100_bib116","doi-asserted-by":"crossref","unstructured":"Seki\n N\n \n \n Toh\n U\n \n \n Sayers\n TJ\n \n \n Fujii\n T\n \n \n Miyagi\n M\n \n \n Akagi\n Y\n \n \n Kusukawa\n J\n \n \n Kage\n M\n \n \n Shirouzu\n K\n \n \n Yamana\n H\n \n \n 2010\n Bortezomib sensitizes human esophageal squamous cell carcinoma cells to TRAIL-mediated apoptosis via activation of both extrinsic and intrinsic apoptosis pathways. Molecular Cancer Therapeutics91842\u20131851. (doi:10.1158\/1535-7163.MCT-09-0918).","DOI":"10.1158\/1535-7163.MCT-09-0918"},{"key":"2026070909024517100_bib117","doi-asserted-by":"crossref","unstructured":"Shah\n MA\n \n \n Power\n DG\n \n \n Kindler\n HL\n \n \n Holen\n KD\n \n \n Kemeny\n MM\n \n \n Ilson\n DH\n \n \n Tang\n L\n \n \n Capanu\n M\n \n \n Wright\n JJ\n \n \n Kelsen\n DP\n \n \n 2011\n A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma. Investigational New Drugs291475\u20131481. (doi:10.1007\/s10637-010-9474-7).","DOI":"10.1007\/s10637-010-9474-7"},{"key":"2026070909024517100_bib118","doi-asserted-by":"crossref","unstructured":"Shanker\n A\n \n \n Brooks\n AD\n \n \n Tristan\n CA\n \n \n Wine\n JW\n \n \n Elliott\n PJ\n \n \n Yagita\n H\n \n \n Takeda\n K\n \n \n Smyth\n MJ\n \n \n Murphy\n WJ\n \n \n Sayers\n TJ\n \n \n 2008\n Treating metastatic solid tumors with bortezomib and a tumor necrosis factor-related apoptosis-inducing ligand receptor agonist antibody. Journal of the National Cancer Institute100649\u2013662. (doi:10.1093\/jnci\/djn113).","DOI":"10.1093\/jnci\/djn113"},{"key":"2026070909024517100_bib119","doi-asserted-by":"crossref","unstructured":"Shen\n M\n \n \n Schmitt\n S\n \n \n Buac\n D\n \n \n Dou\n QP\n \n \n 2013\n Targeting the ubiquitin\u2013proteasome system for cancer therapy. Expert Opinion on Therapeutic Targets171091\u20131108. (doi:10.1517\/14728222.2013.815728).","DOI":"10.1517\/14728222.2013.815728"},{"key":"2026070909024517100_bib120","unstructured":"Shiboski\n CH\n \n \n Schmidt\n BL\n \n \n Jordan\n RC\n \n \n 2005\n Tongue and tonsil carcinoma: increasing trends in the U.S. population ages 20\u201344 years. Cancer1031843\u20131849. (doi:10.1002\/cncr.20998)."},{"key":"2026070909024517100_bib121","doi-asserted-by":"crossref","unstructured":"Siegel\n D\n \n \n Martin\n T\n \n \n Nooka\n A\n \n \n Harvey\n RD\n \n \n Vij\n R\n \n \n Niesvizky\n R\n \n \n Badros\n AZ\n \n \n Jagannath\n S\n \n \n McCulloch\n L\n \n \n Rajangam\n K\n \n \n \n 2013\n Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase 2 clinical studies. Haematologia981753\u20131761. (doi:10.3324\/haematol.2013.089334).","DOI":"10.3324\/haematol.2013.089334"},{"key":"2026070909024517100_bib122","doi-asserted-by":"crossref","unstructured":"Soucy\n TA\n \n \n Smith\n PG\n \n \n Milhollen\n MA\n \n \n Berger\n AJ\n \n \n Gavin\n JM\n \n \n Adhikari\n S\n \n \n Brownell\n JE\n \n \n Burke\n KE\n \n \n Cardin\n DP\n \n \n Critchley\n S\n \n \n \n 2009\n An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature458732\u2013736. (doi:10.1038\/nature07884).","DOI":"10.1038\/nature07884"},{"key":"2026070909024517100_bib123","doi-asserted-by":"crossref","unstructured":"Soucy\n TA\n \n \n Dick\n LR\n \n \n Smith\n PG\n \n \n Milhollen\n MA\n \n \n Brownell\n JE\n \n \n 2010\n The NEDD8 conjugation pathway and its relevance in cancer biology and therapy. Genes & Cancer1708\u2013716. (doi:10.1177\/1947601910382898).","DOI":"10.1177\/1947601910382898"},{"key":"2026070909024517100_bib124","unstructured":"Spratlin\n JL\n \n \n Pitts\n TM\n \n \n Kulikowski\n GN\n \n \n Morelli\n MP\n \n \n Tentler\n JJ\n \n \n Serkova\n NJ\n \n \n Eckhardt\n SG\n \n \n 2011\n Synergistic activity of histone deacetylase and proteasome inhibition against pancreatic and hepatocellular cancer cell lines. Anticancer Research311093\u20131103."},{"key":"2026070909024517100_bib125","unstructured":"Sunwoo\n JB\n \n \n Chen\n Z\n \n \n Dong\n G\n \n \n Yeh\n N\n \n \n Crowl Bancroft\n C\n \n \n Sausville\n E\n \n \n Adams\n J\n \n \n Elliott\n P\n \n \n Van Waes\n C\n \n \n 2001\n Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-\u03baB, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clinical Cancer Research71419\u20131428."},{"key":"2026070909024517100_bib126","doi-asserted-by":"crossref","unstructured":"Terpos\n E\n \n \n Kastritis\n E\n \n \n Roussou\n M\n \n \n Heath\n D\n \n \n Christoulas\n D\n \n \n Anagnostopoulos\n N\n \n \n Eleftherakis-Papaiakovou\n E\n \n \n Tsionos\n K\n \n \n Croucher\n P\n \n \n Dimopoulos\n MA\n \n \n 2008\n The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective regimen for relapsed\/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis. Leukemia222247\u20132256. (doi:10.1038\/leu.2008.235).","DOI":"10.1038\/leu.2008.235"},{"key":"2026070909024517100_bib127","doi-asserted-by":"crossref","unstructured":"Tian\n Z\n \n \n D'Arcy\n P\n \n \n Wang\n X\n \n \n Ray\n A\n \n \n Tai\n YT\n \n \n Hu\n Y\n \n \n Carrasco\n RD\n \n \n Richardson\n P\n \n \n Linder\n S\n \n \n Chauhan\n D\n \n \n \n 2014\n A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood123706\u2013716. (doi:10.1182\/blood-2013-05-500033).","DOI":"10.1182\/blood-2013-05-500033"},{"key":"2026070909024517100_bib128","doi-asserted-by":"crossref","unstructured":"Traenckner\n EB\n \n \n Wilk\n S\n \n \n Baeuerle\n PA\n \n \n 1994\n A proteasome inhibitor prevents activation of NF-\u03baB and stabilizes a newly phosphorylated form of I\u03baB-\u03b1 that is still bound to NF-\u03baB. EMBO Journal135433\u20135441.","DOI":"10.1002\/j.1460-2075.1994.tb06878.x"},{"key":"2026070909024517100_bib129","doi-asserted-by":"crossref","unstructured":"Traenckner\n EB\n \n \n Pahl\n HL\n \n \n Henkel\n T\n \n \n Schmidt\n KN\n \n \n Wilk\n S\n \n \n Baeuerle\n PA\n \n \n 1995\n Phosphorylation of human I\u03baB-\u03b1 on serines 32 and 36 controls I\u03baB-\u03b1 proteolysis and NF-\u03baB activation in response to diverse stimuli. EMBO Journal142876\u20132883.","DOI":"10.1002\/j.1460-2075.1995.tb07287.x"},{"key":"2026070909024517100_bib130","doi-asserted-by":"crossref","unstructured":"Van Waes\n C\n \n \n 2007\n Nuclear factor-\u03baB in development, prevention, and therapy of cancer. Clinical Cancer Research131076\u20131082. (doi:10.1158\/1078-0432.CCR-06-2221).","DOI":"10.1158\/1078-0432.CCR-06-2221"},{"key":"2026070909024517100_bib131","doi-asserted-by":"crossref","unstructured":"Van Waes\n C\n \n \n Chang\n AA\n \n \n Lebowitz\n PF\n \n \n Druzgal\n CH\n \n \n Chen\n Z\n \n \n Elsayed\n YA\n \n \n Sunwoo\n JB\n \n \n Rudy\n SF\n \n \n Morris\n JC\n \n \n Mitchell\n JB\n \n \n \n 2005\n Inhibition of nuclear factor-\u03baB and target genes during combined therapy with proteasome inhibitor bortezomib and reirradiation in patients with recurrent head-and-neck squamous cell carcinoma. International Journal of Radiation Oncology, Biology, Physics631400\u20131412. (doi:10.1016\/j.ijrobp.2005.05.007).","DOI":"10.1016\/j.ijrobp.2005.05.007"},{"key":"2026070909024517100_bib132","doi-asserted-by":"crossref","unstructured":"Vassilev\n LT\n \n \n 2007\n MDM2 inhibitors for cancer therapy. Trends in Molecular Medicine1323\u201331. (doi:10.1016\/j.molmed.2006.11.002).","DOI":"10.1016\/j.molmed.2006.11.002"},{"key":"2026070909024517100_bib133","doi-asserted-by":"crossref","unstructured":"Vassilev\n LT\n \n \n Vu\n BT\n \n \n Graves\n B\n \n \n Carvajal\n D\n \n \n Podlaski\n F\n \n \n Filipovic\n Z\n \n \n Kong\n N\n \n \n Kammlott\n U\n \n \n Lukacs\n C\n \n \n Klein\n C\n \n \n \n 2004\n \n In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science303844\u2013848. (doi:10.1126\/science.1092472).","DOI":"10.1126\/science.1092472"},{"key":"2026070909024517100_bib134","doi-asserted-by":"crossref","unstructured":"Verbrugge\n SE\n \n \n Assaraf\n YG\n \n \n Dijkmans\n BA\n \n \n Scheffer\n GL\n \n \n Al\n M\n \n \n den Uyl\n D\n \n \n Oerlemans\n R\n \n \n Chan\n ET\n \n \n Kirk\n CJ\n \n \n Peters\n GJ\n \n \n \n 2012\n Inactivating PSMB5 mutations and P-glycoprotein (multidrug resistance-associated protein\/ATP-binding cassette B1) mediate resistance to proteasome inhibitors: ex vivo efficacy of (immuno)proteasome inhibitors in mononuclear blood cells from patients with rheumatoid arthritis. Journal of Pharmacological and Experimental Therapeutics341174\u2013182. (doi:10.1124\/jpet.111.187542).","DOI":"10.1124\/jpet.111.187542"},{"key":"2026070909024517100_bib135","doi-asserted-by":"crossref","unstructured":"Voortman\n J\n \n \n Checinska\n A\n \n \n Giaccone\n G\n \n \n Rodriguez\n JA\n \n \n Kruyt\n FA\n \n \n 2007a\n Bortezomib, but not cisplatin, induces mitochondria-dependent apoptosis accompanied by up-regulation of noxa in the non-small cell lung cancer cell line NCI-H460. Molecular Cancer Therapeutics61046\u20131053. (doi:10.1158\/1535-7163.MCT-06-0577).","DOI":"10.1158\/1535-7163.MCT-06-0577"},{"key":"2026070909024517100_bib136","doi-asserted-by":"crossref","unstructured":"Voortman\n J\n \n \n Resende\n TP\n \n \n Abou El Hassan\n MA\n \n \n Giaccone\n G\n \n \n Kruyt\n FA\n \n \n 2007b\n TRAIL therapy in non-small cell lung cancer cells: sensitization to death receptor-mediated apoptosis by proteasome inhibitor bortezomib. Molecular Cancer Therapeutics62103\u20132112. (doi:10.1158\/1535-7163.MCT-07-0167).","DOI":"10.1158\/1535-7163.MCT-07-0167"},{"key":"2026070909024517100_bib137","doi-asserted-by":"crossref","unstructured":"Westra\n WH\n \n \n Taube\n JM\n \n \n Poeta\n ML\n \n \n Begum\n S\n \n \n Sidransky\n D\n \n \n Koch\n WM\n \n \n 2008\n Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clinical Cancer Research14366\u2013369. (doi:10.1158\/1078-0432.CCR-07-1402).","DOI":"10.1158\/1078-0432.CCR-07-1402"},{"key":"2026070909024517100_bib138","unstructured":"Williams\n S\n \n \n Pettaway\n C\n \n \n Song\n R\n \n \n Papandreou\n C\n \n \n Logothetis\n C\n \n \n McConkey\n DJ\n \n \n 2003\n Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts. Molecular Cancer Therapeutics2835\u2013843."},{"key":"2026070909024517100_bib139","doi-asserted-by":"crossref","unstructured":"Yang\n H\n \n \n Zonder\n JA\n \n \n Dou\n QP\n \n \n 2009\n Clinical development of novel proteasome inhibitors for cancer treatment. Expert Opinion on Investigational Drugs18957\u2013971. (doi:10.1517\/13543780903002074).","DOI":"10.1517\/13543780903002074"},{"key":"2026070909024517100_bib140","unstructured":"Yoshiba\n S\n \n \n Iwase\n M\n \n \n Kurihara\n S\n \n \n Uchida\n M\n \n \n Kurihara\n Y\n \n \n Watanabe\n H\n \n \n Shintani\n S\n \n \n 2011\n Proteasome inhibitor sensitizes oral squamous cell carcinoma cells to TRAIL-mediated apoptosis. Oncology Reports25645\u2013652. (doi:10.3892\/or.2010.1127)."},{"key":"2026070909024517100_bib141","doi-asserted-by":"crossref","unstructured":"Yu\n C\n \n \n Rahmani\n M\n \n \n Conrad\n D\n \n \n Subler\n M\n \n \n Dent\n P\n \n \n Grant\n S\n \n \n 2003\n The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr\/Abl+ cells sensitive and resistant to STI571. Blood1023765\u20133774. (doi:10.1182\/blood-2003-03-0737).","DOI":"10.1182\/blood-2003-03-0737"},{"key":"2026070909024517100_bib142","doi-asserted-by":"crossref","unstructured":"Zang\n Y\n \n \n Thomas\n SM\n \n \n Chan\n ET\n \n \n Kirk\n CJ\n \n \n Freilino\n ML\n \n \n DeLancey\n HM\n \n \n Grandis\n JR\n \n \n Li\n C\n \n \n Johnson\n DE\n \n \n 2012a\n Carfilzomib ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy. Clinical Cancer Research185639\u20135649. (doi:10.1158\/1078-0432.CCR-12-1213).","DOI":"10.1158\/1078-0432.CCR-12-1213"},{"key":"2026070909024517100_bib143","doi-asserted-by":"crossref","unstructured":"Zang\n Y\n \n \n Thomas\n SM\n \n \n Chan\n ET\n \n \n Kirk\n CJ\n \n \n Freilino\n ML\n \n \n DeLancey\n HM\n \n \n Grandis\n JR\n \n \n Li\n C\n \n \n Johnson\n DE\n \n \n 2012b\n The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4. Autophagy81873\u20131874. (doi:10.4161\/auto.22185).","DOI":"10.4161\/auto.22185"},{"key":"2026070909024517100_bib144","doi-asserted-by":"crossref","unstructured":"Zhou\n HJ\n \n \n Aujay\n MA\n \n \n Bennett\n MK\n \n \n Dajee\n M\n \n \n Demo\n SD\n \n \n Fang\n Y\n \n \n Ho\n MN\n \n \n Jiang\n J\n \n \n Kirk\n CJ\n \n \n Laidig\n GJ\n \n \n \n 2009\n Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). Journal of Medicinal Chemistry523028\u20133038. (doi:10.1021\/jm801329v).","DOI":"10.1021\/jm801329v"},{"key":"2026070909024517100_bib145","doi-asserted-by":"crossref","unstructured":"Zhu\n H\n \n \n Guo\n W\n \n \n Zhang\n L\n \n \n Wu\n S\n \n \n Teraishi\n F\n \n \n Davis\n JJ\n \n \n Dong\n F\n \n \n Fang\n B\n \n \n 2005a\n Proteasome inhibitors-mediated TRAIL resensitization and Bik accumulation. Cancer Biology & Therapy4781\u2013786. (doi:10.4161\/cbt.4.7.1897).","DOI":"10.4161\/cbt.4.7.1897"},{"key":"2026070909024517100_bib146","doi-asserted-by":"crossref","unstructured":"Zhu\n H\n \n \n Zhang\n L\n \n \n Dong\n F\n \n \n Guo\n W\n \n \n Wu\n S\n \n \n Teraishi\n F\n \n \n Davis\n JJ\n \n \n Chiao\n PJ\n \n \n Fang\n B\n \n \n 2005b\n Bik\/NBK accumulation correlates with apoptosis-induction by bortezomib (PS-341, Velcade) and other proteasome inhibitors. Oncogene244993\u20134999. (doi:10.1038\/sj.onc.1208683).","DOI":"10.1038\/sj.onc.1208683"},{"key":"2026070909024517100_bib147","doi-asserted-by":"crossref","unstructured":"Zhu\n K\n \n \n Dunner\n K\n Jr\n \n \n McConkey\n DJ\n \n \n 2009\n Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells. Oncogene29451\u2013462. (doi:10.1038\/onc.2009.343).","DOI":"10.1038\/onc.2009.343"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/22\/1\/T1.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article-pdf\/22\/1\/T1\/186472\/t1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article-pdf\/22\/1\/T1\/186472\/t1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:03:08Z","timestamp":1783602188000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article\/22\/1\/T1\/33880\/The-ubiquitin-proteasome-system-opportunities-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,1]]},"references-count":147,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,2,1]]}},"URL":"https:\/\/doi.org\/10.1530\/erc-14-0005","relation":{},"ISSN":["1479-6821","1351-0088"],"issn-type":[{"value":"1479-6821","type":"electronic"},{"value":"1351-0088","type":"print"}],"subject":[],"published":{"date-parts":[[2015,2,1]]}}}