Current Treatment Strategies in Malignant Pleural Mesothelioma with a Treatment Algorithm

Sayan, Mutlay; Eren, Mehmet Fuat; Gupta, Apar; Ohri, Nisha; Kotek, Ayse; Babalıoglu, Ibrahim; Kaplan, Sedenay Oskeroglu; Duran, Ozge; Or, Özlem Derinalp; Cukurcayır, Funda; Kurtul, Neslihan; Bıçakçı, Beyhan Ceylaner; Kütük, Tuğçe; Senyurek, Sukran; Türk, Ali; Jabbour, Salma K.; Atalar, Banu

doi:10.5603/arm.2019.0051

Cited by 11 publications

(9 citation statements)

References 95 publications

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“…Surgical procedures such as extrapleural pneumonectomy (EPP) and pleurectomy/decortication have been proposed as curative or palliative approaches, respectively. 13–15 However, the clinical outcome of the mesothelioma and radical surgery (MARS) trial suggested that EPP within trimodal therapy has no benefit. 16 The benefit of open pleurectomy/decortication in addition to chemotherapy is currently under investigation in the MARS 2 trial.…”

Section: Introductionmentioning

confidence: 99%

“…Radiotherapy primarily has a role in palliation, but has been suggested as an adjuvant to surgery and chemotherapy in multimodality treatment. 13 15 Combination chemotherapy with pemetrexed and cisplatin has remained unchanged as the standard of care since 2003 following a phase III clinical trial demonstrating superiority of the combination over cisplatin alone (median survival 13.3 months vs 10 months). 19 In 2016, a phase III trial of the antivascular endothelial growth factor (anti-VEGF) recombinant antibody, bevacizumab, in combination with standard chemotherapy was shown to increase survival in comparison to chemotherapy alone (18.8 months vs 16.1 months) across all MPM subtypes.…”

Section: Introductionmentioning

confidence: 99%

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Use of preclinical models for malignant pleural mesothelioma

Shamseddin

Obacz

Garnett

et al. 2021

Thorax

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Malignant pleural mesothelioma (MPM) is an aggressive cancer most commonly caused by prior exposure to asbestos. Median survival is 12–18 months, since surgery is ineffective and chemotherapy offers minimal benefit. Preclinical models that faithfully recapitulate the genomic and histopathological features of cancer are critical for the development of new treatments. The most commonly used models of MPM are two-dimensional cell lines established from primary tumours or pleural fluid. While these have provided some important insights into MPM biology, these cell models have significant limitations. In order to address some of these limitations, spheroids and microfluidic chips have more recently been used to investigate the role of the three-dimensional environment in MPM. Efforts have also been made to develop animal models of MPM, including asbestos-induced murine tumour models, MPM-prone genetically modified mice and patient-derived xenografts. Here, we discuss the available in vitro and in vivo models of MPM and highlight their strengths and limitations. We discuss how newer technologies, such as the tumour-derived organoids, might allow us to address the limitations of existing models and aid in the identification of effective treatments for this challenging-to-treat disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Use of preclinical models for malignant pleural mesothelioma

Shamseddin

Obacz

Garnett

et al. 2021

Thorax

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“…Malignant pleural mesothelioma (MPM) is a malignant tumor that originates from mesothelial cells and has an extremely poor prognosis [1][2][3][4]. Although MPM is rarer compared to lung cancer, the number of patients worldwide is predicted to increase in the next decades [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Malignant pleural mesothelioma seldom causes metastasis to other organs but has already progressed widely at the time of diagnosis, and radical surgery is often impossible. However, the clinically available therapies for MPM are extremely limited with few regimens [3,4,8]. Therefore, the development of new therapies for unresectable MPM, especially molecularly targeted ones, is highly desirable.…”

Section: Introductionmentioning

confidence: 99%

Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin

Nishinaga

Sato

Yasui

et al. 2020

Cells

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Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody–photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM.

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“…Diagnosis is based on testing of multiple immunohistochemical (IHC) markers of biopsies or cytological samples, and soluble biomarker analysis of pleural effusion to distinguish MPM from other lung malignancies [ 9 ]. The optimal treatment is surgery in combination with chemotherapy and radiotherapy, or both [ 10 ]. Most patients present with a pleural effusion as first symptom and cytological diagnosis increases the chance for earlier diagnosis and prolongs patient survival [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Multiplex Soluble Biomarker Analysis from Pleural Effusion

2020

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Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.

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Current Treatment Strategies in Malignant Pleural Mesothelioma with a Treatment Algorithm

Cited by 11 publications

References 95 publications

Use of preclinical models for malignant pleural mesothelioma

Use of preclinical models for malignant pleural mesothelioma

Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin

Multiplex Soluble Biomarker Analysis from Pleural Effusion

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