open access

Vol 88, No 4 (2020)
REVIEWS
Published online: 2020-07-15
Submitted: 2020-04-19
Accepted: 2020-05-12
Get Citation

New horizons from novel therapies in malignant pleural mesothelioma

Mutlay Sayan, Swati Mamidanna, Mehmet Fuat Eren, Vasudev Daliparty, Teuta Zoto Mustafayev, Carl Nelson, Nisha Ohri, Salma K Jabbour, Aslihan Guven Mert, Banu Atalar
DOI: 10.5603/ARM.a2020.0103
·
Pubmed: 32869268
·
Adv Respir Med 2020;88(4):343-351.

open access

Vol 88, No 4 (2020)
REVIEWS
Published online: 2020-07-15
Submitted: 2020-04-19
Accepted: 2020-05-12

Abstract

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.

Abstract

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.

Get Citation

Keywords

Mesothelioma; chemotherapy; radiotherapy; targeted therapy; immunotherapy

About this article
Title

New horizons from novel therapies in malignant pleural mesothelioma

Journal

Advances in Respiratory Medicine

Issue

Vol 88, No 4 (2020)

Pages

343-351

Published online

2020-07-15

DOI

10.5603/ARM.a2020.0103

Pubmed

32869268

Bibliographic record

Adv Respir Med 2020;88(4):343-351.

Keywords

Mesothelioma
chemotherapy
radiotherapy
targeted therapy
immunotherapy

Authors

Mutlay Sayan
Swati Mamidanna
Mehmet Fuat Eren
Vasudev Daliparty
Teuta Zoto Mustafayev
Carl Nelson
Nisha Ohri
Salma K Jabbour
Aslihan Guven Mert
Banu Atalar

References (99)
  1. Kameda T, Takahashi K, Kim R, et al. Asbestos: use, bans and disease burden in Europe. Bull World Health Organ. 2014; 92(11): 790–797.
  2. Olsen NJ, Franklin PJ, Reid A, et al. Increasing incidence of malignant mesothelioma after exposure to asbestos during home maintenance and renovation. Med J Aust. 2011; 195(5): 271–274.
  3. Carbone M, Yang H. Mesothelioma: recent highlights. Ann Transl Med. 2017; 5(11): 238.
  4. Carbone M, Adusumilli PS, Alexander HR, et al. Mesothelioma: scientific clues for prevention, diagnosis, and therapy. CA Cancer J Clin. 2019; 69(5): 402–429.
  5. Cao C, Tian DH, Pataky KA, et al. Systematic review of pleurectomy in the treatment of malignant pleural mesothelioma. Lung Cancer. 2013; 81(3): 319–327.
  6. Rena O, Casadio C. Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: a harmful procedure. Lung Cancer. 2012; 77(1): 151–155.
  7. Baas P, Fennell D, Kerr KM, et al. ESMO Guidelines Committee. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26 Suppl 5: v31–v39.
  8. Pan HY, Jiang S, Sutton J, et al. Early experience with intensity modulated proton therapy for lung-intact mesothelioma: A case series. Pract Radiat Oncol. 2015; 5(4): e345–e353.
  9. Dumane V, Yorke E, Rimner A, et al. SU-E-T-595: comparison of volumetric modulated arc therapy (VMAT) and static intensity modulated radiotherapy (IMRT) for malignant pleural mesothelioma in patients with intact lungs/post pleurectomy. Medical Physics. 2012; 39(6Part19): 3842–3842.
  10. Lang-Lazdunski L, Bille A, Papa S, et al. Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma. J Thorac Oncol. 2011; 6(10): 1746–1752.
  11. Verma V, Wegner R, Brooks E, et al. Chemotherapy versus supportive care for unresected malignant pleural mesothelioma. Clinical Lung Cancer. 2019; 20(4): 263–269.
  12. Zalcman G, Mazieres J, Margery J, et al. French Cooperative Thoracic Intergroup (IFCT). 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(10026): 1405–1414.
  13. Arrieta O, López-Macías D, Mendoza-García VO, et al. A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma. Cancer Chemother Pharmacol. 2014; 73(5): 975–982.
  14. Katirtzoglou N, Gkiozos I, Makrilia N, et al. Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study. Clin Lung Cancer. 2010; 11(1): 30–35.
  15. Seshacharyulu P, Ponnusamy MP, Haridas D, et al. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012; 16(1): 15–31.
  16. Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel). 2017; 9(5).
  17. Yewale C, Baradia D, Vhora I, et al. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials. 2013; 34(34): 8690–8707.
  18. Mezzapelle R, Miglio U, Rena O, et al. Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma. Br J Cancer. 2013; 108(8): 1743–1749.
  19. Rena O, Boldorini LR, Gaudino E, et al. Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations. J Surg Oncol. 2011; 104(6): 701–705.
  20. Agarwal V, Lind MJ, Cawkwell L. Targeted epidermal growth factor receptor therapy in malignant pleural mesothelioma: where do we stand? Cancer Treat Rev. 2011; 37(7): 533–542.
  21. Enomoto Y, Kasai T, Takeda M, et al. Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma. J Clin Pathol. 2012; 65(6): 522–527.
  22. Forloni M, Gupta R, Nagarajan A, et al. Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells. Cell Rep. 2016; 16(2): 457–471.
  23. Zimmermann M, Zouhair A, Azria D, et al. The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications. Radiat Oncol. 2006; 1: 11.
  24. Gulbins E, Kolesnick R. Raft ceramide in molecular medicine. Oncogene. 2003; 22(45): 7070–7077.
  25. She Y, Lee F, Chen J, et al. The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 selectively potentiates radiation response of human tumors in nude mice, with a marked improvement in therapeutic index. Clin Cancer Res. 2003; 9(10 Pt 1): 3773–3778.
  26. Barbieri F, Würth R, Favoni RE, et al. Receptor tyrosine kinase inhibitors and cytotoxic drugs affect pleural mesothelioma cell proliferation: insight into EGFR and ERK1/2 as antitumor targets. Biochem Pharmacol. 2011; 82(10): 1467–1477.
  27. Govindan R, Kratzke RA, Herndon JE, et al. Cancer and Leukemia Group B (CALGB 30101). Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B. Clin Cancer Res. 2005; 11(6): 2300–2304.
  28. Schildgen V, Pabst O, Tillmann RL, et al. Low frequency of EGFR mutations in pleural mesothelioma patients, Cologne, Germany. Appl Immunohistochem Mol Morphol. 2015; 23(2): 118–125.
  29. Agatsuma N, Yasuda Y, Ozasa H. Malignant pleural mesothelioma harboring both G719C and S768I mutations of EGFR successfully treated with afatinib. J Thorac Oncol. 2017; 12(9): e141–e143.
  30. Burgess AW, Cho HS, Eigenbrot C, et al. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Mol Cell. 2003; 12(3): 541–552.
  31. Kurai J, Chikumi H, Hashimoto K, et al. Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma. Int J Oncol. 2012; 41(5): 1610–1618.
  32. Talavera A, Friemann R, Gómez-Puerta S, et al. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res. 2009; 69(14): 5851–5859.
  33. van Zandwijk N, Pavlakis N, Kao SC, 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(10): 1386–1396.
  34. Reid G, Pel ME, Kirschner MB, et al. Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma. Ann Oncol. 2013; 24(12): 3128–3135.
  35. Liu F, Yang X, Geng M, et al. Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy. Acta Pharm Sin B. 2018; 8(4): 552–562.
  36. Sturm OE, Orton R, Grindlay J, et al. The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier. Sci Signal. 2010; 3(153): ra90.
  37. Shukla A, Hillegass JM, MacPherson MB, et al. ERK2 is essential for the growth of human epithelioid malignant mesotheliomas. Int J Cancer. 2011; 129(5): 1075–1086.
  38. Ramos-Nino ME, Timblin CR, Mossman BT. Mesothelial cell transformation requires increased AP-1 binding activity and ERK-dependent Fra-1 expression. Cancer Res. 2002; 62(21): 6065–6069.
  39. Yan Y, Black CP, Cowan KH. Irradiation-induced G2/M checkpoint response requires ERK1/2 activation. Oncogene. 2007; 26(32): 4689–4698.
  40. Jost M, Huggett TM, Kari C, et al. Epidermal growth factor receptor-dependent control of keratinocyte survival and Bcl-xL expression through a MEK-dependent pathway. J Biol Chem. 2001; 276(9): 6320–6326.
  41. Clark CJ, McDade DM, O'Shaughnessy CT, et al. Contrasting roles of neuronal Msk1 and Rsk2 in Bad phosphorylation and feedback regulation of Erk signalling. J Neurochem. 2007; 102(4): 1024–1034.
  42. Jiang W, Jin G, Cai F, et al. Extracellular signal-regulated kinase 5 increases radioresistance of lung cancer cells by enhancing the DNA damage response. Exp Mol Med. 2019; 51(2): 1–20.
  43. Thompson JK, Shukla A, Leggett AL, et al. Extracellular signal regulated kinase 5 and inflammasome in progression of mesothelioma. Oncotarget. 2018; 9(1): 293–305.
  44. Salaroglio IC, Campia I, Kopecka J, et al. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma. Oncotarget. 2015; 6(2): 1128–1142.
  45. Jamil M, Jerome M, Miley D, et al. A pilot study of zoledronic acid in the treatment of patients with advanced malignant pleural mesothelioma. Lung Cancer: Targets and Therapy. 2017; Volume 8: 39–44.
  46. Li C, Rezov V, Joensuu E, et al. Pirfenidone decreases mesothelioma cell proliferation and migration via inhibition of ERK and AKT and regulates mesothelioma tumor microenvironment in vivo. Sci Rep. 2018; 8(1): 10070.
  47. Eguchi R, Fujimori Y, Takeda H, et al. Arsenic trioxide induces apoptosis through JNK and ERK in human mesothelioma cells. J Cell Physiol. 2011; 226(3): 762–768.
  48. You M, Varona-Santos J, Singh S, et al. Targeting of the Hedgehog signal transduction pathway suppresses survival of malignant pleural mesothelioma cells in vitro. J Thorac Cardiovasc Surg. 2014; 147(1): 508–516.
  49. Slee EA, Lu X. Requirement for phosphorylation of P53 at Ser312 in suppression of chemical carcinogenesis. Sci Rep. 2013; 3: 3105.
  50. Steven A, Seliger B. Control of CREB expression in tumors: from molecular mechanisms and signal transduction pathways to therapeutic target. Oncotarget. 2016; 7(23): 35454–35465.
  51. Wen AY, Sakamoto KM, Miller LS. The role of the transcription factor CREB in immune function. J Immunol. 2010; 185(11): 6413–6419.
  52. Wang F, Marshall CB, Ikura M. Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition. Cell Mol Life Sci. 2013; 70(21): 3989–4008.
  53. Thakur JK, Yadav A, Yadav G. Molecular recognition by the KIX domain and its role in gene regulation. Nucleic Acids Res. 2014; 42(4): 2112–2125.
  54. Pigazzi M, Manara E, Bresolin S, et al. MicroRNA-34b promoter hypermethylation induces CREB overexpression and contributes to myeloid transformation. Haematologica. 2013; 98(4): 602–610.
  55. Suarez CD, Deng X, Hu CD. Targeting CREB inhibits radiation-induced neuroendocrine differentiation and increases radiation-induced cell death in prostate cancer cells. Am J Cancer Res. 2014; 4(6): 850–861.
  56. Deng X, Liu H, Huang J, et al. Ionizing radiation induces prostate cancer neuroendocrine differentiation through interplay of CREB and ATF2: implications for disease progression. Cancer Res. 2008; 68(23): 9663–9670.
  57. Sakamoto KM, Frank DA. CREB in the pathophysiology of cancer: implications for targeting transcription factors for cancer therapy. Clin Cancer Res. 2009; 15(8): 2583–2587.
  58. Shukla A, Bosenberg MW, MacPherson MB, et al. Activated cAMP response element binding protein is overexpressed in human mesotheliomas and inhibits apoptosis. Am J Pathol. 2009; 175(5): 2197–2206.
  59. Westbom CM, Shukla A, MacPherson MB, et al. CREB-induced inflammation is important for malignant mesothelioma growth. Am J Pathol. 2014; 184(10): 2816–2827.
  60. D'Auria F, Centurione L, Centurione MA, et al. Regulation of cancer cell responsiveness to ionizing radiation treatment by cyclic AMP response element binding nuclear transcription factor. Front Oncol. 2017; 7: 76.
  61. Cataldi A, di Giacomo V, Rapino M, et al. Cyclic nucleotide Response Element Binding protein (CREB) activation promotes survival signal in human K562 erythroleukemia cells exposed to ionising radiation/etoposide combined treatment. J Radiat Res. 2006; 47(2): 113–120.
  62. Sayan M, Shukla A, MacPherson MB, et al. Extracellular signal-regulated kinase 5 and cyclic AMP response element binding protein are novel pathways inhibited by vandetanib (ZD6474) and doxorubicin in mesotheliomas. Am J Respir Cell Mol Biol. 2014; 51(5): 595–603.
  63. Li BX, Gardner R, Xue C, et al. Systemic Inhibition of CREB is Well-tolerated in vivo. Sci Rep. 2016; 6: 34513.
  64. Xie F, Fan Q, Li BX, et al. Discovery of a Synergistic Inhibitor of cAMP-Response Element Binding Protein (CREB)-Mediated Gene Transcription with -. J Med Chem. 2019; 62(24): 11423–11429.
  65. Nitulescu GM, Van De Venter M, Nitulescu G, et al. The Akt pathway in oncology therapy and beyond (Review). Int J Oncol. 2018; 53(6): 2319–2331.
  66. Song M, Bode AM, Dong Z, et al. AKT as a therapeutic target for cancer. Cancer Res. 2019; 79(6): 1019–1031.
  67. Rodgers SJ, Ferguson DT, Mitchell CA, et al. Regulation of PI3K effector signalling in cancer by the phosphoinositide phosphatases. Biosci Rep. 2017; 37(1).
  68. Dobbin ZC, Landen CN. The importance of the PI3K/AKT/MTOR pathway in the progression of ovarian cancer. Int J Mol Sci. 2013; 14(4): 8213–8227.
  69. Zhao GX, Pan H, Ouyang DY, et al. The critical molecular interconnections in regulating apoptosis and autophagy. Ann Med. 2015; 47(4): 305–315.
  70. Wang Qi, Chen X, Hay N. Akt as a target for cancer therapy: more is not always better (lessons from studies in mice). Br J Cancer. 2017; 117(2): 159–163.
  71. Xia Pu, Xu XY. PI3K/Akt/mTOR signaling pathway in cancer stem cells: from basic research to clinical application. Am J Cancer Res. 2015; 5(5): 1602–1609.
  72. Milella M, Falcone I, Conciatori F, et al. PTEN: Multiple Functions in Human Malignant Tumors. Front Oncol. 2015; 5: 24.
  73. Li HF, Kim JS, Waldman T. Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells. Radiat Oncol. 2009; 4: 43.
  74. Toulany M, Iida M, Keinath S, et al. Dual targeting of PI3K and MEK enhances the radiation response of K-RAS mutated non-small cell lung cancer. Oncotarget. 2016; 7(28): 43746–43761.
  75. Suzuki Y, Murakami H, Kawaguchi K, et al. Activation of the PI3K-AKT pathway in human malignant mesothelioma cells. Mol Med Rep. 2009; 2(2): 181–188.
  76. Varghese S, Chen Z, Bartlett DL, et al. Activation of the phosphoinositide-3-kinase and mammalian target of rapamycin signaling pathways are associated with shortened survival in patients with malignant peritoneal mesothelioma. Cancer. 2011; 117(2): 361–371.
  77. Zhou S, Liu L, Li H, et al. Multipoint targeting of the PI3K/mTOR pathway in mesothelioma. Br J Cancer. 2014; 110(10): 2479–2488.
  78. Yamada T, Amann JM, Fukuda K, et al. Akt Kinase-Interacting Protein 1 Signals through CREB to Drive Diffuse Malignant Mesothelioma. Cancer Res. 2015; 75(19): 4188–4197.
  79. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12(4): 252–264.
  80. Sul J, Blumenthal GM, Jiang X, et al. FDA approval summary: pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1. Oncologist. 2016; 21(5): 643–650.
  81. Mansfield A, Roden A, Peikert T, et al. B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. Journal of Thoracic Oncology. 2014; 9(7): 1036–1040.
  82. Cedrés S, Ponce-Aix S, Zugazagoitia J, et al. Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM). PLoS One. 2015; 10(3): e0121071.
  83. Garon EB, Rizvi NA, Hui R, et al. KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015; 372(21): 2018–2028.
  84. Alley EW, Lopez J, Santoro A, 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(5): 623–630.
  85. Quispel-Janssen J, van der Noort V, de Vries JF, et al. Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma. J Thorac Oncol. 2018; 13(10): 1569–1576.
  86. Okada M, Kijima T, Aoe 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). Clinical Cancer Research. 2019; 25(18): 5485–5492.
  87. Hassan R, Thomas A, Nemunaitis JJ, 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(3): 351–357.
  88. Fennell DA, Kirkpatrick E, Cozens K, 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(1): 233.
  89. Wolchok JD, Weber JS, Maio M, et al. Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials. Ann Oncol. 2013; 24(8): 2174–2180.
  90. Ribas A, Camacho LH, Lopez-Berestein G, et al. Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol. 2005; 23(35): 8968–8977.
  91. Calabrò L, Morra A, Fonsatti E, et al. Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2013; 14(11): 1104–1111.
  92. Calabrò L, Morra A, Fonsatti E, 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(4): 301–309.
  93. Maio M, Scherpereel A, Calabrò L, 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. The Lancet Oncology. 2017; 18(9): 1261–1273.
  94. Scherpereel A, Mazieres J, Greillier L, 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. The Lancet Oncology. 2019; 20(2): 239–253.
  95. Calabrò L, Morra A, Giannarelli D, 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(6): 451–460.
  96. Disselhorst MJ, Quispel-Janssen J, Lalezari F, 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(3): 260–270.
  97. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012; 12(4): 265–277.
  98. Cornelissen R, Hegmans JP, Maat AP, 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(9): 1023–1031.
  99. Aerts JG, de Goeje PL, Cornelissen R, et al. Autologous dendritic cells pulsed with allogeneic tumor cell lysate in mesothelioma: from mouse to human. Clin Cancer Res. 2018; 24(4): 766–776.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Czasopismo Pneumonologia i Alergologia Polska dostęne jest również w Ikamed - księgarnia medyczna

Wydawcą serwisu jest "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl