Biological basis for novel mesothelioma therapies.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
14
01
2021
accepted:
02
06
2021
revised:
13
05
2021
pubmed:
7
7
2021
medline:
18
12
2021
entrez:
6
7
2021
Statut:
ppublish
Résumé
Mesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies.
Identifiants
pubmed: 34226685
doi: 10.1038/s41416-021-01462-2
pii: 10.1038/s41416-021-01462-2
pmc: PMC8505556
doi:
Substances chimiques
Asbestos
1332-21-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1039-1055Subventions
Organisme : Medical Research Council
ID : G1002610
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R009120/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S005579/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V028669/1
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
Références
Beckett P, Edwards J, Fennell D, Hubbard R, Woolhouse I, Peake MD. Demographics, management and survival of patients with malignant pleural mesothelioma in the National Lung Cancer Audit in England and Wales. Lung Cancer. 2015;88:344–8.
pubmed: 25863904
doi: 10.1016/j.lungcan.2015.03.005
van Zandwijk N, Clarke C, Henderson D, Musk AW, Fong K, Nowak A, et al. Guidelines for the diagnosis and treatment of malignant pleural mesothelioma. J Thorac Dis. 2013;5:E254–307.
pubmed: 24416529
pmcid: 3886874
Schramm A, Opitz I, Thies S, Seifert B, Moch H, Weder W, et al. Prognostic significance of epithelial-mesenchymal transition in malignant pleural mesothelioma. Eur J Cardiothorac Surg. 2010;37:566–72.
pubmed: 19781955
doi: 10.1016/j.ejcts.2009.08.027
Bozzi F, Brich S, Dagrada GP, Negri T, Conca E, Cortelazzi B, et al. Epithelioid peritoneal mesothelioma: a hybrid phenotype within a mesenchymal-epithelial/epithelial-mesenchymal transition framework. Oncotarget. 2016;7:75503–17.
pubmed: 27705913
pmcid: 5342756
doi: 10.18632/oncotarget.12262
Fassina A, Cappellesso R, Guzzardo V, Dalla Via L, Piccolo S, Ventura L, et al. Epithelial-mesenchymal transition in malignant mesothelioma. Mod Pathol. 2012;25:86–99.
pubmed: 21983934
doi: 10.1038/modpathol.2011.144
Ceresoli GL, Locati LD, Ferreri AJ, Cozzarini C, Passoni P, Melloni G, et al. Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma. Lung Cancer. 2001;34:279–87.
pubmed: 11679187
doi: 10.1016/S0169-5002(01)00257-4
Fennell DA, Parmar A, Shamash J, Evans MT, Sheaff MT, Sylvester R, et al. Statistical validation of the EORTC prognostic model for malignant pleural mesothelioma based on three consecutive phase II trials. J Clin Oncol. 2005;23:184–9.
pubmed: 15625372
doi: 10.1200/JCO.2005.07.050
Dalton LE, Clarke HJ, Knight J, Lawson MH, Wason J, Lomas DA, et al. The endoplasmic reticulum stress marker CHOP predicts survival in malignant mesothelioma. Br J Cancer. 2013;108:1340–7.
pubmed: 23412101
pmcid: 3619254
doi: 10.1038/bjc.2013.66
Dell’Anno I, Barone E, Mutti L, Rassl DM, Marciniak SJ, Silvestri R, et al. Tissue expression of lactate transporters (MCT1 and MCT4) and prognosis of malignant pleural mesothelioma (brief report). J Transl Med. 2020;18:341.
pubmed: 32887638
pmcid: 7650278
doi: 10.1186/s12967-020-02487-6
Chia PL, Russell P, Asadi K, Thapa B, Gebski V, Murone C, et al. Analysis of angiogenic and stromal biomarkers in a large malignant mesothelioma cohort. Lung Cancer. 2020;150:1–8.
pubmed: 33035778
doi: 10.1016/j.lungcan.2020.09.022
Schramm A, Opitz I, Thies S, Seifert B, Moch H, Weder W, et al. Prognostic significance of epithelial–mesenchymal transition in malignant pleural mesothelioma. Eur J Cardiothorac Surg. 2010;37:566–72.
pubmed: 19781955
doi: 10.1016/j.ejcts.2009.08.027
Milano MT, Zhang H. Malignant pleural mesothelioma: a population-based study of survival. J Thorac Oncol. 2010;5:1841–8.
pubmed: 20975379
doi: 10.1097/JTO.0b013e3181f1cf2b
Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636–44.
pubmed: 12860938
doi: 10.1200/JCO.2003.11.136
Ivanov SV, Miller J, Lucito R, Tang C, Ivanova AV, Pei J, et al. Genomic events associated with progression of pleural malignant mesothelioma. Int J Cancer. 2009;124:589–99.
pubmed: 18973227
pmcid: 2933144
doi: 10.1002/ijc.23949
Guo G, Chmielecki J, Goparaju C, Heguy A, Dolgalev I, Carbone M, et al. Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma. Cancer Res. 2015;75:264–9.
pubmed: 25488749
doi: 10.1158/0008-5472.CAN-14-1008
Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48:407–16.
pubmed: 26928227
doi: 10.1038/ng.3520
Illei PB, Rusch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res. 2003;9:2108–13.
pubmed: 12796375
Thurneysen C, Opitz I, Kurtz S, Weder W, Stahel RA, Felley-Bosco E. Functional inactivation of NF2/merlin in human mesothelioma. Lung Cancer. 2009;64:140–7.
pubmed: 18835652
doi: 10.1016/j.lungcan.2008.08.014
Bott M, Brevet M, Taylor BS, Shimizu S, Ito T, Wang L, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43:668–72.
pubmed: 21642991
pmcid: 4643098
doi: 10.1038/ng.855
Kato S, Tomson BN, Buys TP, Elkin SK, Carter JL, Kurzrock R. Genomic landscape of malignant mesotheliomas. Mol Cancer Ther. 2016;15:2498–507.
pubmed: 27507853
doi: 10.1158/1535-7163.MCT-16-0229
Hmeljak J, Sanchez-Vega F, Hoadley KA, Shih J, Stewart C, Heiman D, et al. Integrative molecular characterization of malignant pleural mesothelioma. Cancer Discov. 2018;8:1548–65.
pubmed: 30322867
pmcid: 6310008
doi: 10.1158/2159-8290.CD-18-0804
Carbone M, Yang H, Pass HI, Krausz T, Testa JR, Gaudino G. BAP1 and cancer. Nat Rev Cancer. 2013;13:153–9.
pubmed: 23550303
pmcid: 3792854
doi: 10.1038/nrc3459
Carbone M, Harbour JW, Brugarolas J, Bononi A, Pagano I, Dey A, et al. Biological mechanisms and clinical significance of BAP1 mutations in human cancer. Cancer Discov. 2020;10:1103–20.
pubmed: 32690542
pmcid: 8006752
doi: 10.1158/2159-8290.CD-19-1220
Carbone M, Adusumilli PS, Alexander HR Jr, Baas P, Bardelli F, Bononi A, et al. Mesothelioma: scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019;69:402–29.
pubmed: 31283845
pmcid: 8192079
doi: 10.3322/caac.21572
Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43:1022–5.
pubmed: 21874000
pmcid: 3184199
doi: 10.1038/ng.912
Pastorino S, Yoshikawa Y, Pass HI, Emi M, Nasu M, Pagano I, et al. A subset of mesotheliomas with improved survival occurring in carriers of BAP1 and other germline mutations. J Clin Oncol. 2018;36:JCO2018790352.
Baumann F, Flores E, Napolitano A, Kanodia S, Taioli E, Pass H, et al. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival. Carcinogenesis. 2015;36:76–81.
pubmed: 25380601
doi: 10.1093/carcin/bgu227
Carbone M, Arron ST, Beutler B, Bononi A, Cavenee W, Cleaver JE, et al. Tumour predisposition and cancer syndromes as models to study gene-environment interactions. Nat Rev Cancer. 2020;20:533–49.
pubmed: 32472073
pmcid: 8104546
doi: 10.1038/s41568-020-0265-y
Bononi A, Giorgi C, Patergnani S, Larson D, Verbruggen K, Tanji M, et al. BAP1 regulates IP3R3-mediated Ca(2+) flux to mitochondria suppressing cell transformation. Nature. 2017;546:549–53.
pubmed: 28614305
pmcid: 5581194
doi: 10.1038/nature22798
Napolitano A, Pellegrini L, Dey A, Larson D, Tanji M, Flores EG, et al. Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma. Oncogene. 2016;35:1996–2002.
pubmed: 26119930
doi: 10.1038/onc.2015.243
Xu J, Kadariya Y, Cheung M, Pei J, Talarchek J, Sementino E, et al. Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma. Cancer Res. 2014;74:4388–97.
pubmed: 24928783
pmcid: 4165574
doi: 10.1158/0008-5472.CAN-14-1328
LaFave LM, Beguelin W, Koche R, Teater M, Spitzer B, Chramiec A, et al. Loss of BAP1 function leads to EZH2-dependent transformation. Nat Med. 2015;21:1344–9.
pubmed: 26437366
pmcid: 4636469
doi: 10.1038/nm.3947
Petrilli AM, Fernandez-Valle C. Role of Merlin/NF2 inactivation in tumor biology. Oncogene. 2016;35:537–48.
pubmed: 25893302
doi: 10.1038/onc.2015.125
Fleury-Feith J, Lecomte C, Renier A, Matrat M, Kheuang L, Abramowski V, et al. Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours. Oncogene. 2003;22:3799–805.
pubmed: 12802287
doi: 10.1038/sj.onc.1206593
Jongsma J, van Montfort E, Vooijs M, Zevenhoven J, Krimpenfort P, van der Valk M, et al. A conditional mouse model for malignant mesothelioma. Cancer Cell. 2008;13:261–71.
pubmed: 18328429
doi: 10.1016/j.ccr.2008.01.030
Sato T, Sekido Y. NF2/Merlin inactivation and potential therapeutic targets in mesothelioma. Int J Mol Sci. 2018;19:988.
Tranchant R, Quetel L, Tallet A, Meiller C, Renier A, de Koning L, et al. Co-occurring mutations of tumor suppressor genes, LATS2 and NF2, in malignant pleural mesothelioma. Clin Cancer Res. 2017;23:3191–202.
pubmed: 28003305
doi: 10.1158/1078-0432.CCR-16-1971
Miyanaga A, Masuda M, Tsuta K, Kawasaki K, Nakamura Y, Sakuma T, et al. Hippo pathway gene mutations in malignant mesothelioma: revealed by RNA and targeted exon sequencing. J Thorac Oncol. 2015;10:844–51.
pubmed: 25902174
doi: 10.1097/JTO.0000000000000493
Zhang WQ, Dai YY, Hsu PC, Wang H, Cheng L, Yang YL, et al. Targeting YAP in malignant pleural mesothelioma. J Cell Mol Med. 2017;21:2663–76.
pubmed: 28470935
pmcid: 5661117
doi: 10.1111/jcmm.13182
Wu H, Wei L, Fan F, Ji S, Zhang S, Geng J, et al. Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis. Nat Commun. 2015;6:6239.
pubmed: 25695629
doi: 10.1038/ncomms7239
Sherr CJ. The INK4a/ARF network in tumour suppression. Nat Rev Mol Cell Biol. 2001;2:731–7.
pubmed: 11584300
doi: 10.1038/35096061
Bonelli MA, Digiacomo G, Fumarola C, Alfieri R, Quaini F, Falco A, et al. Combined inhibition of CDK4/6 and PI3K/AKT/mTOR pathways induces a synergistic anti-tumor effect in malignant pleural mesothelioma cells. Neoplasia. 2017;19:637–48.
pubmed: 28704762
pmcid: 5508477
doi: 10.1016/j.neo.2017.05.003
Marques M, Tranchant R, Risa-Ebri B, Suarez-Solis ML, Fernandez LC, Carrillo-de-Santa-Pau E, et al. Combined MEK and PI3K/p110beta inhibition as a novel targeted therapy for malignant mesothelioma displaying sarcomatoid features. Cancer Res. 2020;80:843–56.
pubmed: 31911549
doi: 10.1158/0008-5472.CAN-19-1633
Blum Y, Meiller C, Quetel L, Elarouci N, Ayadi M, Tashtanbaeva D, et al. Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications. Nat Commun. 2019;10:1333.
pubmed: 30902996
pmcid: 6430832
doi: 10.1038/s41467-019-09307-6
de Reynies A, Jaurand MC, Renier A, Couchy G, Hysi I, Elarouci N, et al. Molecular classification of malignant pleural mesothelioma: identification of a poor prognosis subgroup linked to the epithelial-to-mesenchymal transition. Clin Cancer Res. 2014;20:1323–34.
pubmed: 24443521
doi: 10.1158/1078-0432.CCR-13-2429
Galateau Salle F, Le Stang N, Tirode F, Courtiol P, Nicholson AG, Tsao MS, et al. Comprehensive molecular and pathologic evaluation of transitional mesothelioma assisted by deep learning approach: a multi-institutional study of the International Mesothelioma Panel from the MESOPATH Reference Center. J Thorac Oncol. 2020;15:1037–53.
pubmed: 32165206
doi: 10.1016/j.jtho.2020.01.025
Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell. 2012;150:12–27.
pubmed: 22770212
doi: 10.1016/j.cell.2012.06.013
Vandermeers F, Sriramareddy Neelature, Costa S, Hubaux C, Cosse R, Willems JP. L. The role of epigenetics in malignant pleural mesothelioma. Lung Cancer. 2013;81:311–8.
pubmed: 23790315
doi: 10.1016/j.lungcan.2013.05.014
Kang HC, Kim HK, Lee S, Mendez P, Kim JW, Woodard G, et al. Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas. Oncotarget. 2016;7:8321–31.
pubmed: 26824986
pmcid: 4884995
doi: 10.18632/oncotarget.7032
Paik PK, Krug LM. Histone deacetylase inhibitors in malignant pleural mesothelioma: preclinical rationale and clinical trials. J Thorac Oncol. 2010;5:275–9.
pubmed: 20035240
pmcid: 4052955
doi: 10.1097/JTO.0b013e3181c5e366
Tarasenko N, Nudelman A, Tarasenko I, Entin-Meer M, Hass-Kogan D, Inbal A, et al. Histone deacetylase inhibitors: the anticancer, antimetastatic and antiangiogenic activities of AN-7 are superior to those of the clinically tested AN-9 (Pivanex). Clin Exp Metastasis. 2008;25:703–16.
pubmed: 18506586
doi: 10.1007/s10585-008-9179-x
Martinez-Iglesias O, Ruiz-Llorente L, Sanchez-Martinez R, Garcia L, Zambrano A, Aranda A. Histone deacetylase inhibitors: mechanism of action and therapeutic use in cancer. Clin Transl Oncol. 2008;10:395–8.
pubmed: 18628067
doi: 10.1007/s12094-008-0221-x
Krug LM, Curley T, Schwartz L, Richardson S, Marks P, Chiao J, et al. Potential role of histone deacetylase inhibitors in mesothelioma: clinical experience with suberoylanilide hydroxamic acid. Clin Lung Cancer. 2006;7:257–61.
pubmed: 16512979
doi: 10.3816/CLC.2006.n.003
Krug LM, Kindler HL, Calvert H, Manegold C, Tsao AS, Fennell D, et al. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2015;16:447–56.
pubmed: 25800891
doi: 10.1016/S1470-2045(15)70056-2
Bensaid D, Blondy T, Deshayes S, Dehame V, Bertrand P, Gregoire M, et al. Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma. Clin Epigenetics. 2018;10:79.
pubmed: 29946373
pmcid: 6006850
doi: 10.1186/s13148-018-0517-9
Sacco JJ, Kenyani J, Butt Z, Carter R, Chew HY, Cheeseman LP, et al. Loss of the deubiquitylase BAP1 alters class I histone deacetylase expression and sensitivity of mesothelioma cells to HDAC inhibitors. Oncotarget. 2015;6:13757–71.
pubmed: 25970771
pmcid: 4537048
doi: 10.18632/oncotarget.3765
Amatori S, Papalini F, Lazzarini R, Donati B, Bagaloni I, Rippo MR, et al. Decitabine, differently from DNMT1 silencing, exerts its antiproliferative activity through p21 upregulation in malignant pleural mesothelioma (MPM) cells. Lung Cancer. 2009;66:184–90.
pubmed: 19233506
doi: 10.1016/j.lungcan.2009.01.015
Balatti V, Maniero S, Ferracin M, Veronese A, Negrini M, Ferrocci G, et al. MicroRNAs dysregulation in human malignant pleural mesothelioma. J Thorac Oncol. 2011;6:844–51.
pubmed: 21358347
doi: 10.1097/JTO.0b013e31820db125
Reid G, Pel ME, Kirschner MB, Cheng YY, Mugridge N, Weiss J, et al. Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma. Ann Oncol. 2013;24:3128–35.
pubmed: 24148817
doi: 10.1093/annonc/mdt412
Kubo T, Toyooka S, Tsukuda K, Sakaguchi M, Fukazawa T, Soh J, et al. Epigenetic silencing of microRNA-34b/c plays an important role in the pathogenesis of malignant pleural mesothelioma. Clin Cancer Res. 2011;17:4965–74.
pubmed: 21673066
doi: 10.1158/1078-0432.CCR-10-3040
Xu Y, Zheng M, Merritt RE, Shrager JB, Wakelee HA, Kratzke RA, et al. miR-1 induces growth arrest and apoptosis in malignant mesothelioma. Chest. 2013;144:1632–43.
pubmed: 23828229
pmcid: 4694093
doi: 10.1378/chest.12-2770
Ivanov SV, Goparaju CM, Lopez P, Zavadil J, Toren-Haritan G, Rosenwald S, et al. Pro-tumorigenic effects of miR-31 loss in mesothelioma. J Biol Chem. 2010;285:22809–17.
pubmed: 20463022
pmcid: 2906272
doi: 10.1074/jbc.M110.100354
Cioce M, Ganci F, Canu V, Sacconi A, Mori F, Canino C, et al. Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma. Oncogene. 2014;33:5319–31.
pubmed: 24240684
doi: 10.1038/onc.2013.476
van Zandwijk N, Pavlakis N, Kao SC, Linton A, Boyer MJ, Clarke S, et al. Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study. Lancet Oncol. 2017;18:1386–96.
pubmed: 28870611
doi: 10.1016/S1470-2045(17)30621-6
Lee BY, Timpson P, Horvath LG, Daly RJ. FAK signaling in human cancer as a target for therapeutics. Pharmacol Ther. 2015;146:132–49.
pubmed: 25316657
doi: 10.1016/j.pharmthera.2014.10.001
Kanteti R, Mirzapoiazova T, Riehm JJ, Dhanasingh I, Mambetsariev B, Wang J, et al. Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma. Cancer Biol Ther. 2018;19:316–27.
pubmed: 29303405
pmcid: 5902231
doi: 10.1080/15384047.2017.1416937
Laszlo V, Valko Z, Ozsvar J, Kovacs I, Garay T, Hoda MA, et al. The FAK inhibitor BI 853520 inhibits spheroid formation and orthotopic tumor growth in malignant pleural mesothelioma. J Mol Med (Berl). 2019;97:231–42.
doi: 10.1007/s00109-018-1725-7
Poulikakos PI, Xiao GH, Gallagher R, Jablonski S, Jhanwar SC, Testa JR. Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK. Oncogene. 2006;25:5960–8.
pubmed: 16652148
doi: 10.1038/sj.onc.1209587
Shapiro IM, Kolev VN, Vidal CM, Kadariya Y, Ring JE, Wright Q, et al. Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship. Sci Transl Med. 2014;6:237ra268.
doi: 10.1126/scitranslmed.3008639
Soria JC, Gan HK, Blagden SP, Plummer R, Arkenau HT, Ranson M, et al. A phase I, pharmacokinetic and pharmacodynamic study of GSK2256098, a focal adhesion kinase inhibitor, in patients with advanced solid tumors. Ann Oncol. 2016;27:2268–74.
pubmed: 27733373
doi: 10.1093/annonc/mdw427
Mak G, Soria JC, Blagden SP, Plummer R, Fleming RA, Nebot N, et al. A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours. Br J Cancer. 2019;120:975–81.
pubmed: 30992546
pmcid: 6735221
doi: 10.1038/s41416-019-0452-3
Fennell DA, Baas P, Taylor P, Nowak AK, Gilligan D, Nakano T, et al. Maintenance defactinib versus placebo after first-line chemotherapy in patients with merlin-stratified pleural mesothelioma: COMMAND-a double-blind, randomized, phase II study. J Clin Oncol. 2019;37:790–8.
pubmed: 30785827
doi: 10.1200/JCO.2018.79.0543
Jagadeeswaran R, Ma PC, Seiwert TY, Jagadeeswaran S, Zumba O, Nallasura V, et al. Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma. Cancer Res. 2006;66:352–61.
pubmed: 16397249
doi: 10.1158/0008-5472.CAN-04-4567
Kanteti R, Dhanasingh I, Kawada I, Lennon FE, Arif Q, Bueno R, et al. MET and PI3K/mTOR as a potential combinatorial therapeutic target in malignant pleural mesothelioma. PLoS ONE. 2014;9:e105919.
pubmed: 25221930
pmcid: 4164360
doi: 10.1371/journal.pone.0105919
De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumour angiogenesis. Nat Rev Cancer. 2017;17:457–74.
pubmed: 28706266
doi: 10.1038/nrc.2017.51
Strizzi L, Catalano A, Vianale G, Orecchia S, Casalini A, Tassi G, et al. Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol. 2001;193:468–75.
pubmed: 11276005
doi: 10.1002/path.824
Kumar-Singh S, Weyler J, Martin MJ, Vermeulen PB, Van Marck E. Angiogenic cytokines in mesothelioma: a study of VEGF, FGF-1 and -2, and TGF beta expression. J Pathol. 1999;189:72–78.
pubmed: 10451491
doi: 10.1002/(SICI)1096-9896(199909)189:1<72::AID-PATH401>3.0.CO;2-0
Klominek J, Baskin B, Hauzenberger D. Platelet-derived growth factor (PDGF) BB acts as a chemoattractant for human malignant mesothelioma cells via PDGF receptor beta-integrin alpha3beta1 interaction. Clin Exp Metastasis. 1998;16:529–39.
pubmed: 9872600
doi: 10.1023/A:1006542301794
Kumar-Singh S, Vermeulen PB, Weyler J, Segers K, Weyn B, Van Daele A, et al. Evaluation of tumour angiogenesis as a prognostic marker in malignant mesothelioma. J Pathol. 1997;182:211–6.
pubmed: 9274533
doi: 10.1002/(SICI)1096-9896(199706)182:2<211::AID-PATH834>3.0.CO;2-D
Scagliotti GV, Gaafar R, Nowak AK, Reck M, Tsao AS, van Meerbeeck J, et al. LUME-Meso: design and rationale of the phase III part of a placebo-controlled study of nintedanib and pemetrexed/cisplatin followed by maintenance nintedanib in patients with unresectable malignant pleural mesothelioma. Clin Lung Cancer. 2017;18:589–93.
pubmed: 28690011
doi: 10.1016/j.cllc.2017.03.010
Grosso F, Steele N, Novello S, Nowak AK, Popat S, Greillier L, et al. Nintedanib plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma: phase II results from the randomized, placebo-controlled LUME-Meso trial. J Clin Oncol. 2017;35:3591–3600.
pubmed: 28892431
doi: 10.1200/JCO.2017.72.9012
Garland LL, Chansky K, Wozniak AJ, Tsao AS, Gadgeel SM, Verschraegen CF, et al. Phase II study of cediranib in patients with malignant pleural mesothelioma: SWOG S0509. J Thorac Oncol. 2011;6:1938–45.
pubmed: 21964533
pmcid: 3477852
doi: 10.1097/JTO.0b013e318229586e
Figg WD, Dahut W, Duray P, Hamilton M, Tompkins A, Steinberg SM, et al. A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer. Clin Cancer Res. 2001;7:1888–93.
pubmed: 11448901
Fujii T, Tachibana M, Dhar DK, Ueda S, Kinugasa S, Yoshimura H, et al. Combination therapy with paclitaxel and thalidomide inhibits angiogenesis and growth of human colon cancer xenograft in mice. Anticancer Res. 2003;23:2405–11.
pubmed: 12894521
Buikhuisen WA, Burgers JA, Vincent AD, Korse CM, van Klaveren RJ, Schramel FM, et al. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study. Lancet Oncol. 2013;14:543–51.
pubmed: 23583604
doi: 10.1016/S1470-2045(13)70125-6
Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005;65:4389–4400.
pubmed: 15899831
doi: 10.1158/0008-5472.CAN-04-4409
Tsao AS, Miao J, Wistuba II, Vogelzang NJ, Heymach JV, Fossella, et al. Phase II trial of cediranib in combination with cisplatin and pemetrexed in chemotherapy-naive patients with unresectable malignant pleural mesothelioma (SWOG S0905). J Clin Oncol. 2019;37:2537–47.
pubmed: 31386610
pmcid: 7001793
doi: 10.1200/JCO.19.00269
Chappell NP, Miller CR, Fielden AD, Barnett JC. Is FDA-approved bevacizumab cost-effective when included in the treatment of platinum-resistant recurrent ovarian cancer? J Oncol Pract. 2016;12:e775–783.
pubmed: 27246689
doi: 10.1200/JOP.2015.010470
Murakami S, Saito H, Kondo T, Oshita F, Yamada K. Phase II study of bevacizumab, cisplatin, and pemetrexed in advanced non-squamous non-small cell lung cancer (NS-NSCLC) with EGFR wild-type. J Exp Ther Oncol. 2019;13:131–8.
pubmed: 31881129
Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387:1405–14.
pubmed: 26719230
doi: 10.1016/S0140-6736(15)01238-6
Levin PA, Dowell JE. Spotlight on bevacizumab and its potential in the treatment of malignant pleural mesothelioma: the evidence to date. Onco Targets Ther. 2017;10:2057–66.
pubmed: 28435296
pmcid: 5391166
doi: 10.2147/OTT.S113598
Urra H, Dufey E, Avril T, Chevet E, Hetz C. Endoplasmic reticulum stress and the hallmarks of cancer. Trends Cancer. 2016;2:252–62.
pubmed: 28741511
doi: 10.1016/j.trecan.2016.03.007
Martinotti S, Ranzato E, Burlando B. (-)- Epigallocatechin-3-gallate induces GRP78 accumulation in the ER and shifts mesothelioma constitutive UPR into proapoptotic ER stress. J Cell Physiol. 2018;233:7082–90.
pubmed: 29744892
doi: 10.1002/jcp.26631
Xu D, Yang H, Yang Z, Berezowska S, Gao Y, Liang SQ, et al. Endoplasmic reticulum stress signaling as a therapeutic target in malignant pleural mesothelioma. Cancers (Basel). 2019;11:1502.
Zhang L, Littlejohn JE, Cui Y, Cao X, Peddaboina C, Smythe WR. Characterization of bortezomib-adapted I-45 mesothelioma cells. Mol Cancer. 2010;9:110.
pubmed: 20482802
pmcid: 2882347
doi: 10.1186/1476-4598-9-110
Cerezo M, Lehraiki A, Millet A, Rouaud F, Plaisant M, Jaune E, et al. Compounds triggering ER stress exert anti-melanoma effects and overcome BRAF inhibitor resistance. Cancer Cell. 2016;30:183.
pubmed: 27479035
doi: 10.1016/j.ccell.2016.06.007
Sarkar Bhattacharya S, Thirusangu P, Jin L, Roy D, Jung D, Xiao Y, et al. PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses. Cell Death Dis. 2019;10:725.
pubmed: 31562297
pmcid: 6764980
doi: 10.1038/s41419-019-1916-3
Szlosarek PW, Klabatsa A, Pallaska A, Sheaff M, Smith P, Crook T, et al. In vivo loss of expression of argininosuccinate synthetase in malignant pleural mesothelioma is a biomarker for susceptibility to arginine depletion. Clin Cancer Res. 2006;12:7126–31.
pubmed: 17145837
doi: 10.1158/1078-0432.CCR-06-1101
Szlosarek PW, Steele JP, Nolan L, Gilligan D, Taylor P, Spicer J, et al. Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma: a randomized clinical trial. JAMA Oncol. 2017;3:58–66.
pubmed: 27584578
doi: 10.1001/jamaoncol.2016.3049
Phillips M, Szyszko T, Hall P, Cook GJR, Khadeir R, Steele JPC, et al. Expansion study of ADI-PEG 20, pemetrexed and cisplatin in patients with ASS1-deficient malignant pleural mesothelioma (TRAP). J Clin Oncol. 2017;35:8553–8553.
doi: 10.1200/JCO.2017.35.15_suppl.8553
Yamada N, Oizumi S, Kikuchi E, Shinagawa N, Konishi-Sakakibara J, Ishimine A, et al. CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection. Cancer Immunol Immunother. 2010;59:1543–9.
pubmed: 20567822
doi: 10.1007/s00262-010-0881-6
Hegmans JP, Hemmes A, Hammad H, Boon L, Hoogsteden HC, Lambrecht BN. Mesothelioma environment comprises cytokines and T-regulatory cells that suppress immune responses. Eur Respir J. 2006;27:1086–95.
pubmed: 16540497
doi: 10.1183/09031936.06.00135305
Burt BM, Rodig SJ, Tilleman TR, Elbardissi AW, Bueno R, Sugarbaker DJ. Circulating and tumor-infiltrating myeloid cells predict survival in human pleural mesothelioma. Cancer. 2011;117:5234–44.
pubmed: 21523763
doi: 10.1002/cncr.26143
Anraku M, Cunningham KS, Yun Z, Tsao MS, Zhang L, Keshavjee S, et al. Impact of tumor-infiltrating T cells on survival in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2008;135:823–9.
pubmed: 18374762
doi: 10.1016/j.jtcvs.2007.10.026
Cornelissen R, Lievense LA, Maat AP, Hendriks RW, Hoogsteden HC, Bogers AJ, et al. Ratio of intratumoral macrophage phenotypes is a prognostic factor in epithelioid malignant pleural mesothelioma. PLoS ONE. 2014;9:e106742.
pubmed: 25192022
pmcid: 4156398
doi: 10.1371/journal.pone.0106742
Tazzari M, Brich S, Tuccitto A, Bozzi F, Beretta V, Spagnuolo RD, et al. Complex immune contextures characterise malignant peritoneal mesothelioma: loss of adaptive immunological signature in the more aggressive histological types. J Immunol Res. 2018;2018:5804230.
pubmed: 30510965
pmcid: 6231377
doi: 10.1155/2018/5804230
Fusco N, Vaira V, Righi I, Sajjadi E, Venetis K, Lopez G, et al. Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients. Lung Cancer. 2020;150:53–61.
pubmed: 33065463
doi: 10.1016/j.lungcan.2020.09.026
Robinson BW, Robinson C, Lake RA. Localised spontaneous regression in mesothelioma - possible immunological mechanism. Lung Cancer. 2001;32:197–201.
pubmed: 11325491
doi: 10.1016/S0169-5002(00)00217-8
Luke JJ, Flaherty KT, Ribas A, Long GV. Targeted agents and immunotherapies: optimizing outcomes in melanoma. Nat Rev Clin Oncol. 2017;14:463–82.
pubmed: 28374786
doi: 10.1038/nrclinonc.2017.43
Teachey DT, Hunger SP. Acute lymphoblastic leukaemia in 2017: immunotherapy for ALL takes the world by storm. Nat Rev Clin Oncol. 2018;15:69–70.
pubmed: 29255238
doi: 10.1038/nrclinonc.2017.176
Assi HI, Kamphorst AO, Moukalled NM, Ramalingam SS. Immune checkpoint inhibitors in advanced non-small cell lung cancer. Cancer. 2018;124:248–61.
pubmed: 29211297
doi: 10.1002/cncr.31105
Marcq E, Siozopoulou V, De Waele J, van Audenaerde J, Zwaenepoel K, Santermans E, et al. Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma. Oncoimmunology. 2017;6:e1261241.
pubmed: 28197385
doi: 10.1080/2162402X.2016.1261241
Cedres S, Ponce-Aix S, Zugazagoitia J, Sansano I, Enguita A, Navarro-Mendivil A, et al. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS ONE. 2015;10:e0121071.
pubmed: 25774992
pmcid: 4361537
doi: 10.1371/journal.pone.0121071
Mansfield AS, Roden AC, Peikert T, Sheinin YM, Harrington SM, Krco CJ, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol. 2014;9:1036–40.
pubmed: 24926549
pmcid: 4058651
doi: 10.1097/JTO.0000000000000177
Calabro L, Morra A, Fonsatti E, Cutaia O, Amato G, Giannarelli D, et al. Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2013;14:1104–11.
pubmed: 24035405
doi: 10.1016/S1470-2045(13)70381-4
Calabro L, Morra A, Fonsatti E, Cutaia O, Fazio C, Annesi D, et al. Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. Lancet Respir Med. 2015;3:301–9.
pubmed: 25819643
doi: 10.1016/S2213-2600(15)00092-2
Maio M, Scherpereel A, Calabro L, Aerts J, Cedres Perez S, Bearz A, et al. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017;18:1261–73.
pubmed: 28729154
doi: 10.1016/S1470-2045(17)30446-1
Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017;18:623–30.
pubmed: 28291584
doi: 10.1016/S1470-2045(17)30169-9
Desai A, Karrison T, Rose B, Tan Y, Hill B, Pemberton E, et al. OA08.03 phase II trial of pembrolizumab (NCT02399371) in previously-treated malignant mesothelioma (MM): final analysis. J Thorac Oncol. 2018;13:S339.
doi: 10.1016/j.jtho.2018.08.277
Rivalland G, Kao SC-H, Pavlakis N, Hughes BGM, Thapa B, Pal A, et al. Outcomes of anti-PD-1 therapy in mesothelioma and correlation with PD-L1 expression. J Clin Oncol. 2017;35:8514.
doi: 10.1200/JCO.2017.35.15_suppl.8514
Goto Y, Okada M, Kijima T, Aoe K, Kato T, Fujimoto N, et al. MA 19.01 a phase II study of nivolumab: a multicenter, open-label, single arm study in malignant pleural mesothelioma (MERIT). J Thorac Oncol. 2017;12:S1883.
doi: 10.1016/j.jtho.2017.09.634
Quispel-Janssen J, van der Noort V, de Vries JF, Zimmerman M, Lalezari F, Thunnissen E, et al. Programmed death 1 blockade with nivolumab in patients with recurrent malignant pleural mesothelioma. J Thorac Oncol. 2018;13:1569–76.
pubmed: 29908324
doi: 10.1016/j.jtho.2018.05.038
Fennell DA, Kirkpatrick E, Cozens K, Nye M, Lester J, Hanna G, et al. CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial. Trials. 2018;19:233.
pubmed: 29669604
pmcid: 5907297
doi: 10.1186/s13063-018-2602-y
Nowak A, Kok P, Lesterhuis W, Hughes B, Brown C, Kao S, et al. OA08.02 DREAM - a phase 2 trial of durvalumab with first line chemotherapy in mesothelioma: final result. J Thorac Oncol. 2018;13:S338–S339.
doi: 10.1016/j.jtho.2018.08.276
Hassan R, Thomas A, Nemunaitis JJ, Patel MR, Bennouna J, Chen FL, et al. Efficacy and safety of avelumab treatment in patients with advanced unresectable mesothelioma: phase 1b results from the JAVELIN Solid Tumor Trial. JAMA Oncol. 2019;5:351–7.
pubmed: 30605211
pmcid: 6439847
doi: 10.1001/jamaoncol.2018.5428
Calabro L, Morra A, Giannarelli D, Amato G, D’Incecco A, Covre A, et al. Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. Lancet Respir Med. 2018;6:451–60.
pubmed: 29773326
doi: 10.1016/S2213-2600(18)30151-6
Venkatraman D, Anderson A, Digumarthy S, Lizotte PH, Awad MM. Phase 2 study of tremelimumab plus durvalumab for previously-treated malignant pleural mesothelioma (MPM). J Clin Oncol. 2019;37:8549–8549.
doi: 10.1200/JCO.2019.37.15_suppl.8549
Disselhorst MJ, Quispel-Janssen J, Lalezari F, Monkhorst K, de Vries JF, van der Noort V, et al. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med. 2019;7:260–70.
pubmed: 30660511
doi: 10.1016/S2213-2600(18)30420-X
Scherpereel A, Mazieres J, Greillier L, Lantuejoul S, Do P, Bylicki O, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol. 2019;20:239–53.
pubmed: 30660609
doi: 10.1016/S1470-2045(18)30765-4
Zalcman G, Mazieres J, Greillier L, Lantuejoul S, Dô P, Bylicki O, et al. LBA58_PRSecond or 3rd line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: updated results of the IFCT-1501 MAPS2 randomized phase 2 trial. Ann Oncol. 2017;28:v605–49.
Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397:375–86.
pubmed: 33485464
doi: 10.1016/S0140-6736(20)32714-8
Webster I, Cochrane JW, Burkhardt KR. Immunotherapy with BCG vaccine in 30 cases of mesothelioma. S Afr Med J. 1982;61:277–8.
pubmed: 7058460
Fuge O, Vasdev N, Allchorne P, Green JS. Immunotherapy for bladder cancer. Res Rep Urol. 2015;7:65–79.
pubmed: 26000263
pmcid: 4427258
Li Q, Kawamura K, Yang S, Okamoto S, Kobayashi H, Tada Y, et al. Interferon-beta produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells. PLoS ONE. 2013;8:e72709.
pubmed: 23977343
pmcid: 3745385
doi: 10.1371/journal.pone.0072709
Christmas TI, Manning LS, Garlepp MJ, Musk AW, Robinson BW. Effect of interferon-alpha 2a on malignant mesothelioma. J Interferon Res. 1993;13:9–12.
pubmed: 8454913
doi: 10.1089/jir.1993.13.9
Boutin C, Nussbaum E, Monnet I, Bignon J, Vanderschueren R, Guerin JC, et al. Intrapleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma. Cancer. 1994;74:2460–7.
pubmed: 7923001
doi: 10.1002/1097-0142(19941101)74:9<2460::AID-CNCR2820740912>3.0.CO;2-N
Yanagawa H, Sone S, Fukuta K, Nishioka Y, Ogura T. Local adoptive immunotherapy using lymphokine-activated killer cells and interleukin-2 against malignant pleural mesothelioma: report of two cases. Jpn J Clin Oncol. 1991;21:377–83.
pubmed: 1753419
Astoul P, Picat-Joossen D, Viallat JR, Boutin C. Intrapleural administration of interleukin-2 for the treatment of patients with malignant pleural mesothelioma: a phase II study. Cancer. 1998;83:2099–104.
pubmed: 9827714
doi: 10.1002/(SICI)1097-0142(19981115)83:10<2099::AID-CNCR8>3.0.CO;2-3
Castagneto B, Zai S, Mutti L, Lazzaro A, Ridolfi R, Piccolini E, et al. Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion: Results of a phase II study on 31 consecutive patients. Lung Cancer. 2001;31:303–10.
pubmed: 11165411
doi: 10.1016/S0169-5002(00)00192-6
Ordonez NG. Value of mesothelin immunostaining in the diagnosis of mesothelioma. Mod Pathol. 2003;16:192–7.
pubmed: 12640097
doi: 10.1097/01.MP.0000056981.16578.C3
Tian L, Zeng R, Wang X, Shen C, Lai Y, Wang M, et al. Prognostic significance of soluble mesothelin in malignant pleural mesothelioma: a meta-analysis. Oncotarget. 2017;8:46425–35.
pubmed: 28507279
pmcid: 5542278
doi: 10.18632/oncotarget.17436
Hassan R, Cohen SJ, Phillips M, Pastan I, Sharon E, Kelly RJ, et al. Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers. Clin Cancer Res. 2010;16:6132–8.
pubmed: 21037025
pmcid: 3057907
doi: 10.1158/1078-0432.CCR-10-2275
Hassan R, Kindler HL, Jahan T, Bazhenova L, Reck M, Thomas A, et al. Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin Cancer Res. 2014;20:5927–36.
pubmed: 25231400
pmcid: 4252585
doi: 10.1158/1078-0432.CCR-14-0804
Le DT, Brockstedt DG, Nir-Paz R, Hampl J, Mathur S, Nemunaitis J, et al. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction. Clin Cancer Res. 2012;18:858–68.
pubmed: 22147941
doi: 10.1158/1078-0432.CCR-11-2121
Hassan R, Alley E, Kindler H, Antonia S, Jahan T, Honarmand S, et al. Clinical response of live-attenuated, Listeria monocytogenes expressing mesothelin (CRS-207) with chemotherapy in patients with malignant pleural mesothelioma. Clin Cancer Res. 2019;25:5787–98.
pubmed: 31263030
pmcid: 8132300
doi: 10.1158/1078-0432.CCR-19-0070
Alley EW, Tanvetyanon T, Jahan TM, Gandhi L, Peikert T, Stevenson J, et al. A phase II single-arm study of CRS-207 with pembrolizumab (pembro) in previously treated malignant pleural mesothelioma (MPM). J Clin Oncol. 2019;37:29–29.
doi: 10.1200/JCO.2019.37.8_suppl.29
Hassan R, Bullock S, Premkumar A, Kreitman RJ, Kindler H, Willingham MC, et al. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin Cancer Res. 2007;13:5144–9.
pubmed: 17785569
doi: 10.1158/1078-0432.CCR-07-0869
Hassan R, Miller AC, Sharon E, Thomas A, Reynolds JC, Ling A, et al. Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression. Sci Transl Med. 2013;5:208ra147.
pubmed: 24154601
pmcid: 6369691
doi: 10.1126/scitranslmed.3006941
Zhang J, Khanna S, Jiang Q, Alewine C, Miettinen M, Pastan I, et al. Efficacy of anti-mesothelin immunotoxin RG7787 plus Nab-paclitaxel against mesothelioma patient-derived xenografts and mesothelin as a biomarker of tumor response. Clin Cancer Res. 2017;23:1564–74.
pubmed: 27635089
doi: 10.1158/1078-0432.CCR-16-1667
Amin KM, Litzky LA, Smythe WR, Mooney AM, Morris JM, Mews DJ, et al. Wilms’ tumor 1 susceptibility (WT1) gene products are selectively expressed in malignant mesothelioma. Am J Pathol. 1995;146:344–56.
pubmed: 7856747
pmcid: 1869867
Krug LM, Dao T, Brown AB, Maslak P, Travis W, Bekele S, et al. WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer. Cancer Immunol Immunother. 2010;59:1467–79.
pubmed: 20532500
pmcid: 4004362
doi: 10.1007/s00262-010-0871-8
Okada M, Kijima T, Aoe K, Kato T, Fujimoto N, Nakagawa K, et al. Clinical efficacy and safety of nivolumab: results of a multicenter, open-label, single-arm, Japanese phase II study in malignant pleural mesothelioma (MERIT). Clin Cancer Res. 2019;25:5485–92.
pubmed: 31164373
doi: 10.1158/1078-0432.CCR-19-0103
Hegmans JP, Hemmes A, Aerts JG, Hoogsteden HC, Lambrecht BN. Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells. Am J Respir Crit Care Med. 2005;171:1168–77.
pubmed: 15764728
doi: 10.1164/rccm.200501-057OC
Hegmans JP, Veltman JD, Lambers ME, de Vries IJ, Figdor CG, Hendriks RW, et al. Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma. Am J Respir Crit Care Med. 2010;181:1383–90.
pubmed: 20167848
doi: 10.1164/rccm.200909-1465OC
Cornelissen R, Hegmans JP, Maat AP, Kaijen-Lambers ME, Bezemer K, Hendriks RW, et al. Extended tumor control after dendritic cell vaccination with low-dose cyclophosphamide as adjuvant treatment in patients with malignant pleural mesothelioma. Am J Respir Crit Care Med. 2016;193:1023–31.
pubmed: 26652184
doi: 10.1164/rccm.201508-1573OC
Aerts J, de Goeje PL, Cornelissen R, Kaijen-Lambers MEH, Bezemer K, van der Leest CH, et al. Autologous dendritic cells pulsed with allogeneic tumor cell lysate in mesothelioma: from mouse to human. Clin Cancer Res. 2018;24:766–76.
pubmed: 29233904
doi: 10.1158/1078-0432.CCR-17-2522
Belderbos RA, Baas P, Berardi R, Cornelissen R, Fennell DA, van Meerbeeck JP, et al. A multicenter, randomized, phase II/III study of dendritic cells loaded with allogeneic tumor cell lysate (MesoPher) in subjects with mesothelioma as maintenance therapy after chemotherapy: DENdritic cell Immunotherapy for Mesothelioma (DENIM) trial. Transl Lung Cancer Res. 2019;8:280–5.
pubmed: 31367541
pmcid: 6626859
doi: 10.21037/tlcr.2019.05.05
Fesnak AD, June CH, Levine BL. Engineered T cells: the promise and challenges of cancer immunotherapy. Nat Rev Cancer. 2016;16:566–81.
pubmed: 27550819
pmcid: 5543811
doi: 10.1038/nrc.2016.97
Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood. 2016;127:3312–20.
pubmed: 27207800
pmcid: 4929923
doi: 10.1182/blood-2016-02-629063
Beatty GL, Haas AR, Maus MV, Torigian DA, Soulen MC, Plesa G, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014;2:112–20.
pubmed: 24579088
doi: 10.1158/2326-6066.CIR-13-0170
Maus MV, Haas AR, Beatty GL, Albelda SM, Levine BL, Liu X, et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res. 2013;1:26–31.
pubmed: 24777247
pmcid: 3888798
doi: 10.1158/2326-6066.CIR-13-0006
Klampatsa A, Haas AR, Moon EK, Albelda SM. Chimeric antigen receptor (CAR) T cell therapy for malignant pleural mesothelioma (MPM). Cancers (Basel). 2017;9:115.
Cherkassky L, Morello A, Villena-Vargas J, Feng Y, Dimitrov DS, Jones DR, et al. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest. 2016;126:3130–44.
pubmed: 27454297
pmcid: 4966328
doi: 10.1172/JCI83092
Adusumilli PS, Zauderer MG, Rusch VW, O’Cearbhaill R, Zhu A, Ngai D, et al. Regional delivery of mesothelin-targeted CAR T cells for pleural cancers: safety and preliminary efficacy in combination with anti-PD-1 agent. J Clin Oncol. 2019;37:2511–2511.
doi: 10.1200/JCO.2019.37.15_suppl.2511
Curioni A, Britschgi C, Hiltbrunner S, Bankel L, Gulati P, Weder W, et al. 1226P A phase I clinical trial of malignant pleural mesothelioma treated with locally delivered autologous anti-FAP-targeted CAR T-cells. Ann Oncol. 2019;30:mdz253.
doi: 10.1093/annonc/mdz253.052
Hiltbrunner S, Britschgi C, Schuberth P, Bankel L, Nguyen-Kim TDL, Gulati P, et al. Local delivery of CAR T cells targeting fibroblast activation protein is safe in patients with pleural mesothelioma: first report of FAPME, a phase I clinical trial. Ann Oncol. 2021;32:120–1.
pubmed: 33098996
doi: 10.1016/j.annonc.2020.10.474
Klampatsa A, Achkova DY, Davies DM, Parente-Pereira AC, Woodman N, Rosekilly J, et al. Intracavitary ‘T4 immunotherapy’ of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells. Cancer Lett. 2017;393:52–59.
pubmed: 28223167
doi: 10.1016/j.canlet.2017.02.015
Beard RE, Zheng Z, Lagisetty KH, Burns WR, Tran E, Hewitt SM, et al. Multiple chimeric antigen receptors successfully target chondroitin sulfate proteoglycan 4 in several different cancer histologies and cancer stem cells. J Immunother Cancer. 2014;2:25.
pubmed: 25197555
pmcid: 4155770
doi: 10.1186/2051-1426-2-25
Rivera Z, Ferrone S, Wang X, Jube S, Yang H, Pass HI, et al. CSPG4 as a target of antibody-based immunotherapy for malignant mesothelioma. Clin Cancer Res. 2012;18:5352–63.
pubmed: 22893632
pmcid: 3463742
doi: 10.1158/1078-0432.CCR-12-0628
Barabas K, Sizensky JA, Faulk WP. Evidence in support of the plasma membrane as the target for transferrin-adriamycin conjugates in K562 cells. Am J Reprod Immunol. 1991;25:120–3.
pubmed: 1930638
doi: 10.1111/j.1600-0897.1991.tb01078.x
Thomas A, Teicher BA, Hassan R. Antibody-drug conjugates for cancer therapy. Lancet Oncol. 2016;17:e254–e262.
pubmed: 27299281
pmcid: 6601617
doi: 10.1016/S1470-2045(16)30030-4
Xie H, Adjei AA. Antibody-drug conjugates for the therapy of thoracic malignancies. J Thorac Oncol. 2019;14:358–76.
pubmed: 30599202
doi: 10.1016/j.jtho.2018.11.034
Pastan I, Hassan R. Discovery of mesothelin and exploiting it as a target for immunotherapy. Cancer Res. 2014;74:2907–12.
pubmed: 24824231
pmcid: 4062095
doi: 10.1158/0008-5472.CAN-14-0337
Golfier S, Kopitz C, Kahnert A, Heisler I, Schatz CA, Stelte-Ludwig B, et al. Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect. Mol Cancer Ther. 2014;13:1537–48.
pubmed: 24714131
doi: 10.1158/1535-7163.MCT-13-0926
Kindler HL, Novello S, Fennell D, Blumenschein G, Bearz A, Ceresoli G, et al. OA 02.01 randomized phase II study of anetumab ravtansine or vinorelbine in patients with metastatic pleural mesothelioma. J Thorac Oncol. 2017;12:S1746.
doi: 10.1016/j.jtho.2017.09.328
Scales SJ, Gupta N, Pacheco G, Firestein R, French DM, Koeppen H, et al. An antimesothelin-monomethyl auristatin e conjugate with potent antitumor activity in ovarian, pancreatic, and mesothelioma models. Mol Cancer Ther. 2014;13:2630–40.
pubmed: 25249555
doi: 10.1158/1535-7163.MCT-14-0487-T
Weekes CD, Lamberts LE, Borad MJ, Voortman J, McWilliams RR, Diamond JR, et al. Phase I study of DMOT4039A, an antibody-drug conjugate targeting mesothelin, in patients with unresectable pancreatic or platinum-resistant ovarian cancer. Mol Cancer Ther. 2016;15:439–47.
pubmed: 26823490
doi: 10.1158/1535-7163.MCT-15-0693
Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102:1458–65.
pubmed: 12714494
doi: 10.1182/blood-2003-01-0039
Dabir S, Kresak A, Yang M, Fu P, Wildey G, Dowlati A. CD30 is a potential therapeutic target in malignant mesothelioma. Mol Cancer Ther. 2015;14:740–6.
pubmed: 25589494
pmcid: 4456236
doi: 10.1158/1535-7163.MCT-14-0972
van der Weyden CA, Pileri SA, Feldman AL, Whisstock J, Prince HM. Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions. Blood Cancer J. 2017;7:e603.
pubmed: 28885612
pmcid: 5709754
doi: 10.1038/bcj.2017.85
Yi JH, Kim SJ, Kim WS. Brentuximab vedotin: clinical updates and practical guidance. Blood Res. 2017;52:243–53.
pubmed: 29333400
pmcid: 5762734
doi: 10.5045/br.2017.52.4.243
Sharman JP, Wheler JJ, Einhorn L, Dowlati A, Shapiro GI, Hilton J, et al. A phase 2, open-label study of brentuximab vedotin in patients with CD30-expressing solid tumors. Invest New Drugs. 2019;37:738–47.
pubmed: 30993587
pmcid: 6647393
doi: 10.1007/s10637-019-00768-6
Schunselaar LM, Monkhorst K, van der Noort V, Wijdeven R, Peters D, Zwart W, et al. Trophoblast glycoprotein is associated with a favorable outcome for mesothelioma and a target for antibody drug conjugates. J Thorac Oncol. 2018;13:1577–87.
pubmed: 29959059
doi: 10.1016/j.jtho.2018.06.008
Hayashi M, Madokoro H, Yamada K, Nishida H, Morimoto C, Sakamoto M, et al. Novel antibody-drug conjugate with anti-CD26 humanized monoclonal antibody and transcription factor IIH (TFIIH) inhibitor, triptolide, inhibits tumor growth via impairing mRNA synthesis. Cancers (Basel). 2019;11:1138.
Aoe K, Amatya VJ, Fujimoto N, Ohnuma K, Hosono O, Hiraki A, et al. CD26 overexpression is associated with prolonged survival and enhanced chemosensitivity in malignant pleural mesothelioma. Clin Cancer Res. 2012;18:1447–56.
pubmed: 22261805
doi: 10.1158/1078-0432.CCR-11-1990
Zhou ZL, Yang YX, Ding J, Li YC, Miao ZH. Triptolide: structural modifications, structure-activity relationships, bioactivities, clinical development and mechanisms. Nat Prod Rep. 2012;29:457–75.
pubmed: 22270059
doi: 10.1039/c2np00088a
Pease DF, Kratzke RA. Oncolytic viral therapy for mesothelioma. Front Oncol. 2017;7:179.
pubmed: 28884088
pmcid: 5573749
doi: 10.3389/fonc.2017.00179
Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14:642–62.
pubmed: 26323545
pmcid: 7097180
doi: 10.1038/nrd4663
Bommareddy PK, Shettigar M, Kaufman HL. Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol. 2018;18:498–513.
pubmed: 29743717
doi: 10.1038/s41577-018-0014-6
Seymour LW, Fisher KD. Oncolytic viruses: finally delivering. Br J Cancer. 2016;114:357–61.
pubmed: 26766734
pmcid: 4815777
doi: 10.1038/bjc.2015.481
Harrington K, Freeman DJ, Kelly B, Harper J, Soria JC. Optimizing oncolytic virotherapy in cancer treatment. Nat Rev Drug Discov. 2019;18:689–706.
pubmed: 31292532
doi: 10.1038/s41573-019-0029-0
Pimm MV, Baldwin RW. Treatment of transplanted rat tumours with double-stranded RNA(BRL 5907). II. Treatment of pleural and peritoneal growths. Br J Cancer. 1976;33:166–71.
pubmed: 177036
pmcid: 2024947
doi: 10.1038/bjc.1976.21
Smythe WR, Kaiser LR, Hwang HC, Amin KM, Pilewski JM, Eck SJ, et al. Successful adenovirus-mediated gene transfer in an in vivo model of human malignant mesothelioma. Ann Thorac Surg. 1994;57:1395–401.
pubmed: 8010779
doi: 10.1016/0003-4975(94)90090-6
Kuryk L, Haavisto E, Garofalo M, Capasso C, Hirvinen M, Pesonen S, et al. Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model. Int J Cancer. 2016;139:1883–93.
pubmed: 27287512
doi: 10.1002/ijc.30228
Adusumilli PS, Stiles BM, Chan MK, Mullerad M, Eisenberg DP, Ben-Porat L, et al. Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses. J Gene Med. 2006;8:603–15.
pubmed: 16475242
pmcid: 1804293
doi: 10.1002/jgm.877
Li H, Peng KW, Dingli D, Kratzke RA, Russell SJ. Oncolytic measles viruses encoding interferon beta and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy. Cancer Gene Ther. 2010;17:550–8.
pubmed: 20379224
pmcid: 2907639
doi: 10.1038/cgt.2010.10
Kelly KJ, Woo Y, Brader P, Yu Z, Riedl C, Lin SF, et al. Novel oncolytic agent GLV-1h68 is effective against malignant pleural mesothelioma. Hum Gene Ther. 2008;19:774–82.
pubmed: 18754710
pmcid: 2940611
doi: 10.1089/hum.2008.036
Silberhumer GR, Brader P, Wong J, Serganova IS, Gonen M, Gonzalez SJ, et al. Genetically engineered oncolytic Newcastle disease virus effectively induces sustained remission of malignant pleural mesothelioma. Mol Cancer Ther. 2010;9:2761–9.
pubmed: 20858727
pmcid: 3266818
doi: 10.1158/1535-7163.MCT-10-0090
Kawasaki Y, Tamamoto A, Takagi-Kimura M, Maeyama Y, Yamaoka N, Terada N, et al. Replication-competent retrovirus vector-mediated prodrug activator gene therapy in experimental models of human malignant mesothelioma. Cancer Gene Ther. 2011;18:571–8.
pubmed: 21660062
pmcid: 3159547
doi: 10.1038/cgt.2011.25
Comins C, Spicer J, Protheroe A, Roulstone V, Twigger K, White CM, et al. REO-10: a phase I study of intravenous reovirus and docetaxel in patients with advanced cancer. Clin Cancer Res. 2010;16:5564–72.
pubmed: 20926400
pmcid: 3934355
doi: 10.1158/1078-0432.CCR-10-1233
Harada A, Uchino J, Harada T, Nakagaki N, Hisasue J, Fujita M, et al. Vascular endothelial growth factor promoter-based conditionally replicative adenoviruses effectively suppress growth of malignant pleural mesothelioma. Cancer Sci. 2017;108:116–23.
pubmed: 27783867
doi: 10.1111/cas.13112
Takagi-Kimura M, Yamano T, Tamamoto A, Okamura N, Okamura H, Hashimoto-Tamaoki T, et al. Enhanced antitumor efficacy of fiber-modified, midkine promoter-regulated oncolytic adenovirus in human malignant mesothelioma. Cancer Sci. 2013;104:1433–9.
pubmed: 23962292
pmcid: 7654241
doi: 10.1111/cas.12267
Aghi M, Visted T, Depinho RA, Chiocca EA. Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent cells with homozygous genetic mutations in p16. Oncogene. 2008;27:4249–54.
pubmed: 18345032
pmcid: 7100519
doi: 10.1038/onc.2008.53
Li Y, Zhang C, Chen X, Yu J, Wang Y, Yang Y, et al. ICP34.5 protein of herpes simplex virus facilitates the initiation of protein translation by bridging eukaryotic initiation factor 2alpha (eIF2alpha) and protein phosphatase 1. J Biol Chem. 2011;286:24785–92.
pubmed: 21622569
pmcid: 3137054
doi: 10.1074/jbc.M111.232439
Bennett JJ, Adusumilli P, Petrowsky H, Burt BM, Roberts G, Delman KA, et al. Up-regulation of GADD34 mediates the synergistic anticancer activity of mitomycin C and a gamma134.5 deleted oncolytic herpes virus (G207). FASEB J. 2004;18:1001–3.
pubmed: 15059970
doi: 10.1096/fj.02-1080fje
Adusumilli PS, Stiles BM, Chan MK, Chou TC, Wong RJ, Rusch VW, et al. Radiation therapy potentiates effective oncolytic viral therapy in the treatment of lung cancer. Ann Thorac Surg. 2005;80:409–16.
pubmed: 16039175
pmcid: 1373787
doi: 10.1016/j.athoracsur.2005.01.048
Nakashima H, Nguyen T, Kasai K, Passaro C, Ito H, Goins WF, et al. Toxicity and efficacy of a novel GADD34-expressing oncolytic HSV-1 for the treatment of experimental glioblastoma. Clin Cancer Res. 2018;24:2574–84.
pubmed: 29511029
pmcid: 6800093
doi: 10.1158/1078-0432.CCR-17-2954
Sterman DH, Haas A, Moon E, Recio A, Schwed D, Vachani A, et al. A trial of intrapleural adenoviral-mediated Interferon-alpha2b gene transfer for malignant pleural mesothelioma. Am J Respir Crit Care Med. 2011;184:1395–9.
pubmed: 21642245
pmcid: 3262033
doi: 10.1164/rccm.201103-0554CR
Sterman DH, Alley E, Stevenson JP, Friedberg J, Metzger S, Recio A, et al. Pilot and feasibility trial evaluating immuno-gene therapy of malignant mesothelioma using intrapleural delivery of adenovirus-IFNalpha combined with chemotherapy. Clin Cancer Res. 2016;22:3791–3800.
pubmed: 26968202
pmcid: 4970934
doi: 10.1158/1078-0432.CCR-15-2133
Lauer UM, Schell M, Beil J, Berchtold S, Koppenhofer U, Glatzle J, et al. Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis. Clin Cancer Res. 2018;24:4388–98.
pubmed: 29773661
doi: 10.1158/1078-0432.CCR-18-0244
Gilham C, Rake C, Hodgson J, Darnton A, Burdett G, Peto Wild J, et al. Past and current asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS). Int J Epidemiol. 2018;47:1745–56.
pubmed: 29534192
pmcid: 6280925
doi: 10.1093/ije/dyx276
Frank AL, Joshi TK. The global spread of asbestos. Ann Glob Health. 2014;80:257–62.
pubmed: 25459326
doi: 10.1016/j.aogh.2014.09.016
Chernova T, Murphy FA, Galavotti S, Sun XM, Powley IR, Grosso S, et al. Long-fiber carbon nanotubes replicate asbestos-induced mesothelioma with disruption of the tumor suppressor gene Cdkn2a (Ink4a/Arf). Curr Biol. 2017;27:3302.e6–14.e6.
doi: 10.1016/j.cub.2017.09.007
Shamseddin M, Obacz J, Garnett MJ, Rintoul RC, Francies HE, Marciniak SJ. Use of preclinical models for malignant pleural mesothelioma. Thorax. 2021. https://doi.org/10.1136/thoraxjnl-2020-216602.
doi: 10.1136/thoraxjnl-2020-216602.
pubmed: 33692175
Winters NI, Williams AM, Bader DM. Resident progenitors, not exogenous migratory cells, generate the majority of visceral mesothelium in organogenesis. Dev Biol. 2014;391:125–32.
pubmed: 24746591
pmcid: 4037704
doi: 10.1016/j.ydbio.2014.04.003
Dixit R, Ai X, Fine A. Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry. Development. 2013;140:4398–406.
pubmed: 24130328
pmcid: 4007715
doi: 10.1242/dev.098079
Winters N, Bader D. Development of the serosal mesothelium. J Dev Biol. 2013;1:64–81.
doi: 10.3390/jdb1020064
Karki S, Surolia R, Hock TD, Guroji P, Zolak JS, Duggal R, et al. Wilms’ tumor 1 (Wt1) regulates pleural mesothelial cell plasticity and transition into myofibroblasts in idiopathic pulmonary fibrosis. FASEB J. 2014;28:1122–31.
pubmed: 24265486
pmcid: 3929684
doi: 10.1096/fj.13-236828
Rump A, Morikawa Y, Tanaka M, Minami S, Umesaki N, Takeuchi M, et al. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem. 2004;279:9190–8.
pubmed: 14676194
doi: 10.1074/jbc.M312372200
Bera TK, Pastan I. Mesothelin is not required for normal mouse development or reproduction. Mol Cell Biol. 2000;20:2902–6.
pubmed: 10733593
pmcid: 85523
doi: 10.1128/MCB.20.8.2902-2906.2000