The Future of Mesothelioma Research: Basic Science Research

Fear, Vanessa S.; Cook, Alistair; Fisher, Scott

doi:10.1007/978-3-319-96244-3_18

Cited by 2 publications

(14 citation statements)

References 43 publications

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“…Only a select minority of patients are eligible for a complete tumour resection; either via lung-sacrificing surgery, such as an extrapleural pneumonectomy (EPP), or lung-sparing surgery, such as a pleurectomy/decortication (P/D) [119]. EPP surgery is considerably more beneficial than P/D being that it has an associated average overall survival (OS) benefit of 40 months compared to just 23 months for P/D [120]. Despite the evident OS benefit of EPP surgery, the surgical procedure is high-risk and prone to technical complications such as haemorrhage, empyema, atrial fibrillation, and acute respiratory distress syndrome (ARDS); contributing to a 30-day patient mortality rate of 2-5% after EPP surgery [120].…”

Section: Treatment Development 231 Current Standard Of Carementioning

confidence: 99%

“…EPP surgery is considerably more beneficial than P/D being that it has an associated average overall survival (OS) benefit of 40 months compared to just 23 months for P/D [120]. Despite the evident OS benefit of EPP surgery, the surgical procedure is high-risk and prone to technical complications such as haemorrhage, empyema, atrial fibrillation, and acute respiratory distress syndrome (ARDS); contributing to a 30-day patient mortality rate of 2-5% after EPP surgery [120]. Patients with unresectable disease are usually treated with palliative systemic chemotherapy, consisting of 4 to 6 cycles of combination chemotherapy with platinum and antifolates [121].…”

Section: Treatment Development 231 Current Standard Of Carementioning

confidence: 99%

“…In addition to BAP1-targeted strategies, researchers have investigated therapeutic strategies that are specific to the CDKN2A mutation of MPM tumours. CDKN2A encodes the ADP-ribosylation factor (ARF, commonly known as p14) and INK4A (commonly known as p16), and function by regulating the expression of the p53, and pRB tumour suppressors; ultimately leading to G1 arrest and G0 arrest/apoptosis, respectively [120]. The whole INK4a/ARF locus is typically deleted in more than 70% of human mesothelioma cell lines, which is associated with a loss of function of p53 and pRb, and a consequent failure of cell cycle arrest.…”

Section: Targeted Therapiesmentioning

confidence: 99%

“…The aim of neoantigen vaccination is to prime the host immune system to recognise and target the foreign MPM tumour cells. Neoantigens arise as a result of mutations to oncogenes and tumour suppressor genes, oncogenic viruses, oncofoetal proteins, or overexpression of proteins [120]. They constitute attractive candidates for the development of immune-mediated anti-tumour vaccines given that they; (i) exhibit high binding affinities for T cell and human leukocyte antigen (HLA) receptors, (ii) their expression is restricted only to tumour cells, and (iii) their collective binding affinity and specificity effects enable them to bypass central tolerance and issues associated with autoimmunity [204].…”

Section: Immunotherapiesmentioning

confidence: 99%

“…In order to elicit an immune-mediated anti-tumour response, the neoantigens must be presented to T cells upon binding to MHC molecules. Neoantigen vaccination represents a potential form of personalised therapy that is uniquely tailored to individual MPM patients on the basis that their tumour sample can be sequenced using next-generation sequencing (NGS) technology to detect aberrant mutation expression of the neoantigens via RNAseq, and MHC binding potential determined in silico [120,205]. The capacity to identify MPM tumour-specific neoantigens using NGS platforms and capability of vaccinating patients with their own tumour-specific neoantigens has stimulated considerable research interest in anti-cancer vaccination strategies for MPM.…”

Section: Immunotherapiesmentioning

confidence: 99%

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Pre-Clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review

Johnson

Lee

Cheng

2021

Onco

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Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the lung lining that is predominantly associated with occupational exposure to asbestos. MPM is responsible for thousands of deaths worldwide every year, with the median survival of MPM of 8–14 months. There are limited biomarkers available in the clinic to effectively diagnose MPM, an invasive biopsy procedure is usually required to provide a definitive diagnosis. Due to the long latency period associated with MPM disease presentation, the cancer is usually at an advanced stage at the time of diagnosis where treatment options are largely ineffective at controlling disease progression. Previous MPM-based pre-clinical studies have made significant strides in determining the exact molecular mechanisms associated with asbestos carcinogenesis. Exploring less invasive blood-based biomarkers and treatment strategies involving targeted therapy, immunotherapy, and virotherapy is particularly important. Research in these areas is of crucial importance in relation to improving the rate of novel diagnostic biomarkers and treatment strategies progressing through to clinical trials and ultimately into the clinical setting. This review comprehensively summarises both previous and current pre-clinical research developments that have specifically contributed to an improved understanding of MPM disease biology, and the development of novel diagnostic biomarkers and treatment strategies.

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Section: Treatment Development 231 Current Standard Of Carementioning

confidence: 99%

Section: Treatment Development 231 Current Standard Of Carementioning

confidence: 99%

Section: Targeted Therapiesmentioning

confidence: 99%

Section: Immunotherapiesmentioning

confidence: 99%

Section: Immunotherapiesmentioning

confidence: 99%

See 3 more Smart Citations

Pre-Clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review

Johnson

Lee

Cheng

2021

Onco

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Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma – A Review

2021

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Malignant mesothelioma is an aggressive cancer with poor prognosis, predominantly caused by human occupational exposure to asbestos. The global incidence of mesothelioma is predicted to increase as a consequence of continued exposure to asbestos from a variety of sources, including construction material produced in the past in developed countries, as well as those currently being produced in developing countries. Mesothelioma typically develops after a long latency period and consequently it is often diagnosed in the clinic at an advanced stage, at which point standard care of treatment, such as chemo- and radio-therapy, are largely ineffective. Much of our current understanding of mesothelioma biology, particularly in relation to disease pathogenesis, diagnosis and treatment, can be attributed to decades of preclinical basic science research. Given the postulated rising incidence in mesothelioma cases and the limitations of current diagnostic and treatment options, continued preclinical research into mesothelioma is urgently needed. The ever-evolving landscape of preclinical models and laboratory technology available to researchers have made it possible to study human disease with greater precision and at an accelerated rate. In this review article we provide an overview of the various resources that can be exploited to facilitate an enhanced understanding of mesothelioma biology and their applications to research aimed to improve the diagnosis and treatment of mesothelioma. These resources include cell lines, animal models, mesothelioma-specific biobanks and modern laboratory techniques/technologies. Given that different preclinical models and laboratory technologies have varying limitations and applications, they must be selected carefully with respect to the intended objectives of the experiments. This review therefore aims to provide a comprehensive overview of the various preclinical models and technologies with respect to their advantages and limitations. Finally, we will detail about a highly valuable preclinical laboratory resource to curate high quality mesothelioma biospecimens for research; the biobank. Collectively, these resources are essential to the continued advancement of precision medicine to curtail the increasing health burden caused by malignant mesothelioma.

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The Future of Mesothelioma Research: Basic Science Research

Cited by 2 publications

References 43 publications

Pre-Clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review

Pre-Clinical Research Advancements Relating to Improving the Diagnosis and Treatment of Malignant Pleural Mesothelioma: A Review

Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma – A Review

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