scholarly journals Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

2021 ◽  
Vol 10 (11) ◽  
pp. 2290
Author(s):  
Emanuele Vita ◽  
Alessio Stefani ◽  
Mariantonietta Di Di Salvatore ◽  
Marco Chiappetta ◽  
Filippo Lococo ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Genomic Sequencing ◽  
Pleural Mesothelioma ◽  
Targeted Drugs ◽  
Treatment Algorithms ◽  
Rare Malignancy ◽  
New Generation ◽  
The Way

Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.

scholarly journals LOCAL DELIVERY OF TARGETED NANOPARTICLES AS THERAPEUTIC APPROACH TO OBLITERANS BRONCHIOLITIS AND MALIGNANT PLEURAL MESOTHELIOMA

2017 ◽  
Author(s):  
Federica Meloni ◽  
Emanuela Cova ◽  
Davide Piloni ◽  
Simona Inghilleri ◽  
Giulia Maria Stella ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Therapeutic Approach ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Primary Cultures ◽  
Local Treatment ◽  
Target Cells ◽  
Pleural Mesothelioma ◽  
Small Airways

Our work has the objective to develop and provide a new therapeutic approach to rare respiratory disease with poor prognosis. These diseases are united by the fact of being rare diseases, defined orphan, with a very poor prognosis and limited treatment options. Furthermore, they share the possibility to apply a local treatment with the advantage of decreased unwanted biodistribution and systemic toxicity. Bronchiolitis obliterans (BO) is a disease characterized by fibrotic obliteration of the small airways that occurs in response to inflammatory and immunological insults. Malignant pleural mesothelioma (MPM) is a rare malignant tumor that originates from the pleura, strongly associated with environmental exposure to asbestos. Our approach consists in the creation of nanocarriers (gold nanoparticles, GNPs), which can be loaded with specific anti-proliferative drugs, specifically targeted to the cells responsible of the two pathological processes (fibroblastoid-like mesenchymal cells in BO, malignant mesothelioma cells in MPM) and suitable for administration by local street (inhaled or intrapleural). First, we isolated, cultured and phenotyped primary cells from patients from BO and MPM. Once you have identified some targets (CD44 for the BO and CD146 for MPM) we designed a nanotool loaded with the specific drugs (everolimus or pemetrexed) and decorated with monoclonal antibody on the surface. We performed experiments in vitro on primary cultures of pathological cells and we demonstrated that these nanoparticles were able to penetrate specifically in target cells expressing the specific receptor and not in other types of normal cells tested, except for the alveolar macrophage which presented the tendency to absorb the nanoparticles, also the not functionalized ones. The anti-proliferative, pro-apoptotic and anti-inflammatory action of these nanoparticles was tested in vitro. We have also conducted experiments in animals to prove the lack of both pulmonary and extrapulmonary toxicity following administration of nanoparticles by inhalation.

New Era for Malignant Pleural Mesothelioma: Updates on Therapeutic Options

2022 ◽  
Author(s):  
Anne S. Tsao ◽  
Harvey I. Pass ◽  
Andreas Rimner ◽  
Aaron S. Mansfield
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Checkpoint Inhibitors ◽  
Treatment Plan ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Pleural Mesothelioma ◽  
Frontline Treatment ◽  
Rare Malignancy

Malignant pleural mesothelioma (MPM) is a rare malignancy with few treatment options. Recent advances have led to US Food and Drug Administration approvals and changes in the standard of care with a novel biomedical device approved for use with platinum-pemetrexed, and also for immunotherapy agents to be included as a frontline treatment option in unresectable disease. Although predictive biomarkers for systemic therapy are not currently in use in clinical practice, it is essential to correctly identify the MPM histology to determine an optimal treatment plan. Patients with nonepithelioid MPM may have a greater magnitude of benefit to dual immunotherapy checkpoint inhibitors and this regimen should be preferred in the frontline setting for these patients. However, all patients with MPM can derive benefit from immunotherapy treatments, and these agents should ultimately be used at some point during their treatment journey. There are ongoing studies in the frontline unresectable setting that may further define the frontline therapy space, but a critical area of research will need to focus on the immunotherapy refractory population. This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. These recent innovations are generating momentum to find better therapies for this disease.

scholarly journals Hitting the Bull’s-Eye: Mesothelin’s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3932
Author(s):  
Dannel Yeo ◽  
Laura Castelletti ◽  
Nico van Zandwijk ◽  
John E. J. Rasko
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Treatment Options ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Pleural Mesothelioma ◽  
Normal Tissues ◽  
Drug Conjugates ◽  
Aggressive Cancer ◽  
Immunotherapy Target ◽  
Bull's Eye

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options and poor prognosis. MPM originates from the mesothelial lining of the pleura. Mesothelin (MSLN) is a glycoprotein expressed at low levels in normal tissues and at high levels in MPM. Many other solid cancers overexpress MSLN, and this is associated with worse survival rates. However, this association has not been found in MPM, and the exact biological role of MSLN in MPM requires further exploration. Here, we discuss the current research on the diagnostic and prognostic value of MSLN in MPM patients. Furthermore, MSLN has become an attractive immunotherapy target in MPM, where better treatment strategies are urgently needed. Several MSLN-targeted monoclonal antibodies, antibody–drug conjugates, immunotoxins, cancer vaccines, and cellular therapies have been tested in the clinical setting. The biological rationale underpinning MSLN-targeted immunotherapies and their potential to improve MPM patient outcomes are reviewed.

scholarly journals Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma

2018 ◽  
Vol 51 (5) ◽  
pp. 1701610 ◽  
Author(s):  
Takahiko Otsuki ◽  
Taku Nakashima ◽  
Hironobu Hamada ◽  
Yusuke Takayama ◽  
Shin Akita ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Molecular Target ◽  
Aminopeptidase N ◽  
Pleural Mesothelioma ◽  
Tumour Angiogenesis ◽  
Potential Therapeutic Target

Angiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM) and antiangiogenic strategies might be effective against MPM. Aminopeptidase N (APN)/CD13 promotes tumour angiogenesis and is associated with poor prognosis; however, its clinical significance in MPM remains unclear.In 37 consecutive patients with surgically resected MPM, we evaluated the association between immunohistochemical APN/CD13 expression in resected tumours and survival. Additionally, the antitumour and antiangiogenic effects of MT95-4, a fully humanised anti-APN/CD13 monoclonal antibody, were evaluated in mice orthotopically implanted with EHMES-10 (abundantly expressing APN/CD13) and MSTO-211H (scarcely expressing APN/CD13) MPM cells.High tumour APN/CD13 expression was associated with poor prognosis in MPM patients (p=0.04), and MT95-4 treatment reduced tumour growth and angiogenesis in mice harbouring EHMES-10 but not MSTO-211H cells. Furthermore, in mice harbouring EHMES-10 cells, MT95-4 combined with cisplatin more effectively suppressed tumour progression than cisplatin alone.Taken together, these results suggest that APN/CD13 is implicated in the aggressiveness of MPM. Here, MT95-4 treatment reduced tumour progression likely by inhibiting angiogenesis, suggesting APN/CD13 as a potential molecular target for MPM treatment. Additionally, combination treatment with MT95-4 and cisplatin could represent a promising approach to treating MPM exhibiting high APN/CD13 expression.

scholarly journals Treatment of malignant pleural mesothelioma: current status and future directions

2016 ◽  
Vol 73 (2) ◽  
Author(s):  
X. Dhalluin ◽  
A. Scherpereel
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
European Society ◽  
Poor Prognosis ◽  
Asbestos Exposure ◽  
Therapeutic Strategies ◽  
Current Status ◽  
Pleural Mesothelioma ◽  
European Respiratory Society ◽  
Future Directions ◽  
Cell Therapies

Previously considered to be rare, malignant pleural mesothelioma (MPM) is a highly aggressive tumour that has become a very important issue over recent years due to its poor prognosis and its increasing incidence mostly linked to previous asbestos exposure. An optimal treatment for MPM is not established yet; new therapies and predictive tools are still needed in the management of this cancer. Thus the aim of this review is to provide clinicians clear and up-to-dated data on the latest therapeutic strategies for MPM patients in 2010. The guidelines recently proposed by the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) taskforce are summarized here. The authors also briefly reviewed the future directions in MPM treatment including targeted therapies, gene or cell therapies.

scholarly journals Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments

Thorax ◽  
2020 ◽  
Vol 75 (11) ◽  
pp. 1004-1008 ◽  
Author(s):  
Nikolaos I Kanellakis ◽  
Rachelle Asciak ◽  
Megat Abd Hamid ◽  
Xuan Yao ◽  
Mark McCole ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Ex Vivo ◽  
Cytotoxic T Cells ◽  
Pleural Mesothelioma ◽  
Ex Vivo Model ◽  
High Throughput Drug Screening ◽  
Aggressive Cancer ◽  
Malignant Pleural Mesothelioma Cell

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

Circulating tumor cell (CTC) as a significant clinical marker in epithelioid-type malignant pleural mesothelioma (MPM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7080-7080
Author(s):  
Kazue Yoneda ◽  
Fumihiro Tanaka ◽  
Shunichi Fukuda ◽  
Hayato Orui ◽  
Masaki Hashimoto ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Tumor Cell ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Circulating Tumor Cell ◽  
Independent Prognostic Factor ◽  
Pleural Mesothelioma ◽  
Roc Curve Analysis ◽  
Clinical Marker ◽  
Significant Difference

7080 Background: Circulating tumor cell (CTC) is a surrogate of distant metastasis, and our preliminary study suggested that CTC detected by an EpCAM-based immuno-magnetic separation system (“CellSearch”) was a useful clinical marker in the diagnosis of malignant pleural mesothelioma (MPM) (Tanaka F. et al ASCO 2008). Methods: Patients who presented at our institute to receive pleural biopsy with suspicion of MPM were prospectively enrolled. CTCs in 7.5mL of peripheral blood were quantitatively evaluated with the CellSearch system. Results: Among 136 eligible patients, 104 were finally diagnosed with MPM, and 32 were with non-malignant diseases (NM). CTC was positive (CTC≥1) in 32.7% (37/104) of MPM pts, and in 9.4% (3/32) of NM pts (p=0.011). CTC-count was significantly higher in MPM (range, 0-9) than in NM (range, 0-1; p=0.007). According to a ROC curve analysis, the CTC-test provided a significant diagnostic performance in discrimination between MPM and NM (AUC= 0.623; P=0.036). Among MPM pts, CTC-positivity and CTC-count were significantly increased with tumor progression (p=0.026 and p=0.008, respectively). For all MPM pts, there was no significant difference in overall survival between CTC-positive and negative pts. However, in a planned subset analysis, CTC was a significant factor to predict poor prognosis (median survival time, 8.0 months for CTC-positive pts, and 20.3 months for negative pts; p=0.012) in pts with epithelioid-type MPM in which CTC was exclusively positive; a multivariate analysis confirmed that CTC, along with PS, was an independent prognostic factor (HR=2.38; P=0.006). Conclusions: CTC was a significant diagnostic marker in discrimination between MPM and NM. CTC-positivity was a significant and independent prognostic factor to predict a poor prognosis of epithelioid MPM. [Table: see text]

Epigenetic down-regulation of integrin α7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma

2015 ◽  
Vol 237 (2) ◽  
pp. 203-214 ◽  
Author(s):  
Viktoria Laszlo ◽  
Mir Alireza Hoda ◽  
Tamas Garay ◽  
Christine Pirker ◽  
Bahil Ghanim ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Pleural Mesothelioma ◽  
Down Regulation
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