The Biology of Malignant Mesothelioma and the Relevance of Preclinical Models

Malignant mesothelioma (MM), especially its more frequent form, malignant pleural mesothelioma (MPM), is a devastating thoracic cancer with limited therapeutic options. Recently, clinical trials that used immunotherapy strategies have yielded promising results, but the benefits are restricted to a limited number of patients. To develop new therapeutic strategies and define predictors of treatment response to existing therapy, better knowledge of the cellular and molecular mechanisms of MM tumors and sound preclinical models are needed. This review aims to provide an overview of our present knowledge and issues on both subjects. MM shows a complex pattern of molecular changes, including genetic, chromosomic, and epigenetic alterations. MM is also a heterogeneous cancer. The recently described molecular classifications for MPM could better consider inter-tumor heterogeneity, while histo-molecular gradients are an interesting way to consider both intra- and inter-tumor heterogeneities. Classical preclinical models are based on use of MM cell lines in culture or implanted in rodents, i.e., xenografts in immunosuppressed mice or isografts in syngeneic rodents to assess the anti-tumor immune response. Recent developments are tumoroids, patient-derived xenografts (PDX), xenografts in humanized mice, and genetically modified mice (GEM) that carry mutations identified in human MM tumor cells. Multicellular tumor spheroids are an interesting in vitro model to reduce animal experimentat...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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Patients with mesothelioma are being recruited by the National Cancer Institute for a phase II clinical trial using a novel immunotoxin prior to pembrolizumab, a combination that has shown preliminary evidence of efficacy. This promising mesothelioma clinical trial involves the drug LMB-100, designed to make immunotherapy agents such as pembrolizumab, otherwise known as Keytruda, more effective. NCI’s trial includes separate cohorts for pleural and peritoneal types of mesothelioma. “This is a very good option for these patients,” medical oncologist Dr. Raffit Hassan, an acclaimed investigator at the Natio...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Researchers at UCLA Jonsson Comprehensive Cancer Center will soon begin studying the pre-surgery use of cryoablation as a potential early adjuvant therapy for patients with pleural mesothelioma. The pilot study will measure immune system stimulation through local tumor infiltration in hopes of extending patient survival in the future. Cryoablation, also known as cryotherapy or cryosurgery, freezes localized tumors with liquid nitrogen or argon gas. It has been proven effective in killing tumor cells with extreme cold. It is currently used on kidney, liver and prostate cancers, but its use in priming a person’s own i...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Study statistics show the benefits of the novel transarterial chemoperfusion treatment being used successfully at the Moffitt Cancer Center in Tampa for patients with relapsed pleural mesothelioma. Russell Lamkins — working on the roof of a neighbor’s house — shows them even better. He is living proof. This latest mesothelioma treatment has potential. Lamkins, 73, was first diagnosed with mesothelioma in 2014. He was the second patient to enroll in the mesothelioma clinical trial in March 2016, soon after standard-of-care chemotherapy and immunotherapy had failed him. “At that point, I had no choice...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Patients with pleural mesothelioma cancer may have another treatment option after the U.S. Food and Drug Administration approved the use of pembrolizumab for certain metastatic tumors this week. Pembrolizumab, often known by the brand name Keytruda, is a well-known immunotherapy drug already being used with mixed success for several cancers. This latest FDA approval is for the treatment of adult and pediatric cancers with unresectable disease and high mutational burden that have progressed following prior treatment and have no alternative treatment options. A number of mesothelioma patients already are being treated with p...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
(Johns Hopkins Medicine) Inoperable malignant pleural mesothelioma, is a rare and aggressive cancer of the protective lining of the lungs, or pleura, often caused by exposure to asbestos.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009–2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multi...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: ERS/ESTS/EACTS/ESTRO guidelines Source Type: research
Patients with pleural mesothelioma cancer experienced a significant survival advantage when ramucirumab, a novel immunotherapy drug, was added to chemotherapy in a treatment regimen. Ramucirumab, marketed by Eli Lilly and Company as Cyramza, is a monoclonal antibody that works by targeting and restricting a protein that stimulates blood vessel growth within tumors. An ongoing phase II clinical trial in Italy recently reported almost double overall survival rates when ramucirumab was added to gemcitabine in second-line mesothelioma treatment. “These positive data may be the beginning to change the clinical practice in...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Malignant pleural mesothelioma (MPM) is a treatment recalcitrant tumor with a poor overall survival (OS). Current approved treatment consists of first line chemotherapy that only modestly increases OS, illustrating the desperate need for other treatment options in MPM. Unfortunately, clinical studies that investigate the effectivity of checkpoint inhibitor (CI) treatment failed to improve clinical outcome over current applied therapies. In general, MPM is characterized as an immunological cold tumor with low T-cell infiltration, which could explain the disappointing results of clinical trials investigating CI treatment in ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
An international, much-anticipated phase III clinical trial that could change standard-of-care treatment for patients with malignant pleural mesothelioma will open soon, pending COVID-19 pandemic restrictions. The randomized trial will be studying the effectiveness of the immunotherapy drug durvalumab (Imfinzi) when used in combination with chemotherapy drugs pemetrexed (Alimta) and cisplatin for mesothelioma. Opening dates may vary by center because of the COVID-19 pandemic that has slowed or stalled clinical trials everywhere. Durvalumab produces an antibody that helps a patient’s own immune system kill tumor cell...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Conclusions: Since its introduction, PERCIST 1.0 has been increasingly used in many clinical trials and prospective studies, with variable reporting of metabolic response and survival data. In general, it appears PERCIST response is associated with longer PFS and survival though the heterogeneity of disease, scan timing and therapies make data pooling difficult. Prospective inclusion of the PERCIST 1.0 criteria in clinical trials using FDG, with baseline, early monitoring, and end of therapy scans could inform cancer clinical trials. Support: 5U01CA140204-04 Reference: 1. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: NET and Others II Source Type: research
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