Emerging Treatments for Malignant Pleural Mesothelioma: Where Are We Heading?

Overview

Journal Front Oncol

Specialty Oncology

Date 2020 Apr 1

PMID 32226777

Citations 31

Authors

Luca Cantini

Raffit Hassan

Daniel H Sterman

Joachim G J V Aerts

Affiliations

Soon will be listed here.

Abstract

Malignant pleural mesothelioma (MPM) is an uncommon but aggressive and treatment resistant neoplasm with low survival rates. In the last years we assisted to an exponential growth in the appreciation of mesothelioma pathobiology, leading several new treatments to be investigated both in the early stage of the disease and in the advanced setting. In particular, expectations are now high that immunotherapy will have a leading role in the next years. However, caution is required as results from phase II studies in MPM were often not replicated in larger, randomized, phase III trials. In this review, we describe the most promising emerging therapies for the treatment of MPM, discussing the biological rationale underlying their development as well as the issues surrounding clinical trial design and proper selection of patients for every treatment.

Citing Articles

Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review).

Andreikos D, Spandidos D, Georgakopoulou V Int J Oncol. 2025; 66(3).

PMID: 39981889 PMC: 11844339. DOI: 10.3892/ijo.2025.5729.

Transfer learning approach in pre-treatment CT images to predict therapeutic response in advanced malignant pleural mesothelioma.

Fanizzi A, Catino A, Bove S, Comes M, Montrone M, Sicolo A Front Oncol. 2024; 14:1432188.

PMID: 39351354 PMC: 11439621. DOI: 10.3389/fonc.2024.1432188.

Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment.

Karatkevich D, Losmanova T, Zens P, Deng H, Dubey C, Zhang T Sci Rep. 2024; 14(1):18206.

PMID: 39107509 PMC: 11303810. DOI: 10.1038/s41598-024-69347-x.

[Advances in Targeted Therapy for Malignant Pleural Mesothelioma].

Fu F, Zhang Y, Shen H Zhongguo Fei Ai Za Zhi. 2024; 27(5):391-398.

PMID: 38880927 PMC: 11183316. DOI: 10.3779/j.issn.1009-3419.2024.102.18.

PD-L1 expression complements CALGB prognostic scoring system in malignant pleural mesothelioma.

Aviles-Salas A, Cabrera-Miranda L, Hernandez-Pedro N, Vargas-Lias D, Samtani S, Munoz-Montano W Front Oncol. 2023; 13:1269029.

PMID: 38111532 PMC: 10725960. DOI: 10.3389/fonc.2023.1269029.

References

Bueno R, Stawiski E, Goldstein L, Durinck S, De Rienzo A, Modrusan Z . Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016; 48(4):407-16. DOI: 10.1038/ng.3520. View

Strizzi L, Catalano A, Vianale G, Orecchia S, Casalini A, Tassi G . Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma. J Pathol. 2001; 193(4):468-75. DOI: 10.1002/path.824. View

LaFave L, Beguelin W, Koche R, Teater M, Spitzer B, Chramiec A . Loss of BAP1 function leads to EZH2-dependent transformation. Nat Med. 2015; 21(11):1344-9. PMC: 4636469. DOI: 10.1038/nm.3947. View

Hassan R, Alley E, Kindler H, Antonia S, Jahan T, Honarmand S . Clinical Response of Live-Attenuated, Expressing Mesothelin (CRS-207) with Chemotherapy in Patients with Malignant Pleural Mesothelioma. Clin Cancer Res. 2019; 25(19):5787-5798. PMC: 8132300. DOI: 10.1158/1078-0432.CCR-19-0070. View

Delage B, Fennell D, Nicholson L, McNeish I, Lemoine N, Crook T . Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer. 2010; 126(12):2762-72. DOI: 10.1002/ijc.25202. View

Pease D, Kratzke R . Oncolytic Viral Therapy for Mesothelioma. Front Oncol. 2017; 7:179. PMC: 5573749. DOI: 10.3389/fonc.2017.00179. View

Belderbos R, Baas P, Berardi R, Cornelissen R, Fennell D, van Meerbeeck J . 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(3):280-285. PMC: 6626859. DOI: 10.21037/tlcr.2019.05.05. View

Baas P, Fennell D, Kerr K, Van Schil P, Haas R, Peters S . Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26 Suppl 5:v31-9. DOI: 10.1093/annonc/mdv199. View

Mansfield A, Roden A, Peikert T, Sheinin Y, Harrington S, Krco C . B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis. J Thorac Oncol. 2014; 9(7):1036-1040. PMC: 4058651. DOI: 10.1097/JTO.0000000000000177. View

10.

Peto J, Decarli A, La Vecchia C, Levi F, Negri E . The European mesothelioma epidemic. Br J Cancer. 1999; 79(3-4):666-72. PMC: 2362439. DOI: 10.1038/sj.bjc.6690105. View

11.

Metaxas Y, Fruh M, Eboulet E, Grosso F, Pless M, Zucali P . Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16). Ann Oncol. 2020; 31(4):495-500. DOI: 10.1016/j.annonc.2019.12.009. View

12.

Cornelissen R, Lievense L, Maat A, Hendriks R, Hoogsteden H, Bogers A . Ratio of intratumoral macrophage phenotypes is a prognostic factor in epithelioid malignant pleural mesothelioma. PLoS One. 2014; 9(9):e106742. PMC: 4156398. DOI: 10.1371/journal.pone.0106742. View

13.

Flores R, Pass H, Seshan V, Dycoco J, Zakowski M, Carbone M . Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008; 135(3):620-6, 626.e1-3. DOI: 10.1016/j.jtcvs.2007.10.054. View

14.

Fujimoto N, Aoe K, Kozuki T, Oze I, Kato K, Kishimoto T . A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol. Clin Lung Cancer. 2018; 19(5):e705-e707. DOI: 10.1016/j.cllc.2018.05.001. View

15.

Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D . 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. DOI: 10.1016/S0140-6736(15)01238-6. View

16.

Calabro L, Morra A, Cornelissen R, Aerts J, Maio M . Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge. Cancer Immunol Immunother. 2018; 67(8):1317-1324. PMC: 11028073. DOI: 10.1007/s00262-018-2191-3. View

17.

Ohar J, Cheung M, Talarchek J, Howard S, Howard T, Hesdorffer M . Germline BAP1 Mutational Landscape of Asbestos-Exposed Malignant Mesothelioma Patients with Family History of Cancer. Cancer Res. 2016; 76(2):206-15. PMC: 4715907. DOI: 10.1158/0008-5472.CAN-15-0295. View

18.

Patel M, Jacobson B, Ji Y, Drees J, Tang S, Xiong K . Vesicular stomatitis virus expressing interferon-β is oncolytic and promotes antitumor immune responses in a syngeneic murine model of non-small cell lung cancer. Oncotarget. 2015; 6(32):33165-77. PMC: 4741756. DOI: 10.18632/oncotarget.5320. View

19.

Kameda T, Takahashi K, Kim R, Jiang Y, Movahed M, Park E . Asbestos: use, bans and disease burden in Europe. Bull World Health Organ. 2014; 92(11):790-7. PMC: 4221761. DOI: 10.2471/BLT.13.132118. View

20.

Enk A, Jonuleit H, Saloga J, Knop J . Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int J Cancer. 1997; 73(3):309-16. DOI: 10.1002/(sici)1097-0215(19971104)73:3<309::aid-ijc1>3.0.co;2-3. View