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

Onco ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 49-82
Author(s):  
Ben Johnson ◽  
Kenneth Lee ◽  
Yuen Yee Cheng
Keyword(s):  
Clinical Research ◽  
Malignant Pleural Mesothelioma ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Latency Period ◽  
Pleural Mesothelioma ◽  
Diagnostic Biomarkers ◽  
Disease Biology ◽  
Long Latency

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.

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 MicroRNA Expression in Malignant Pleural Mesothelioma and Asbestosis: A Pilot Study

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Mozzoni ◽  
Luca Ampollini ◽  
Matteo Goldoni ◽  
Rossella Alinovi ◽  
Marcello Tiseo ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Molecular Mechanisms ◽  
Prognostic Biomarkers ◽  
Pleural Mesothelioma ◽  
Diagnostic Biomarkers ◽  
Asbestos Fibers ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Patient Prognosis

Background. The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression.Aims. To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients.Methods. miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients.Conclusions. All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.

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 The Evolving Landscape of the Molecular Epidemiology of Malignant Pleural Mesothelioma

2021 ◽  
Vol 10 (5) ◽  
pp. 1034
Author(s):  
Sara Lettieri ◽  
Chandra Bortolotto ◽  
Francesco Agustoni ◽  
Filippo Lococo ◽  
Andrea Lancia ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Malignant Pleural Mesothelioma ◽  
Strong Association ◽  
Pleural Mesothelioma ◽  
The European Union ◽  
Long Latency ◽  
Substantial Risk ◽  
Novel Biomarkers ◽  
Definition Of ◽  
Novel Concept

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. It has a strong association with exposure to biopersistent fibers, mainly asbestos (80% of cases) and—in specific geographic regions—erionite, zeolites, ophiolites, and fluoro-edenite. Individuals with a chronic exposure to asbestos generally have a long latency with no or few symptoms. Then, when patients do become symptomatic, they present with advanced disease and a worse overall survival (about 13/15 months). The fibers from industrial production not only pose a substantial risk to workers, but also to their relatives and to the surrounding community. Modern targeted therapies that have shown benefit in other human tumors have thus far failed in MPM. Overall, MPM has been listed as orphan disease by the European Union. However, molecular high-throughput profiling is currently unveiling novel biomarkers and actionable targets. We here discuss the natural evolution, mainly focusing on the novel concept of molecular epidemiology. The application of innovative endpoints, quantification of genetic damages, and definition of genetic susceptibility are reviewed, with the ultimate goal to point out new tools for screening of exposed subject and for designing more efficient diagnostic and therapeutic strategies.

scholarly journals Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1548
Author(s):  
Mustafa N. Mithaiwala ◽  
Danielle Santana-Coelho ◽  
Grace A. Porter ◽  
Jason C. O’Connor
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Kynurenine Pathway ◽  
Economic Problem ◽  
Cns Disease ◽  
Therapeutic Implications ◽  
Efficacious Treatment ◽  
The Central Nervous System ◽  
Significant Health

Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsychiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, infections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that ‘fuel the fire’ in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.

scholarly journals Myeloma Bone Disease: Update on Pathogenesis and Novel Treatment Strategies

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 202 ◽  
Author(s):  
Sonia Vallet ◽  
Julia-Marie Filzmoser ◽  
Martin Pecherstorfer ◽  
Klaus Podar
Keyword(s):  
Bone Disease ◽  
Molecular Mechanisms ◽  
Bone Fractures ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Nf Kappa B ◽  
Skeletal Involvement ◽  
Myeloma Bone Disease ◽  
Skeletal Related Events ◽  
Novel Treatment Strategies

Bone disease, including osteolytic lesions and/or osteoporosis, is a common feature of multiple myeloma (MM). The consequences of skeletal involvement are severe pain, spinal cord compressions, and bone fractures, which have a dramatic impact on patients’ quality of life and, ultimately, survival. During the past few years, several landmark studies significantly enhanced our insight into MM bone disease (MBD) by identifying molecular mechanisms leading to increased bone resorption due to osteoclast activation, and decreased bone formation by osteoblast inhibition. Bisphosphonates were the mainstay to prevent skeletal-related events in MM for almost two decades. Excitingly, the most recent approval of the receptor activator of NF-kappa B ligand (RANKL) inhibitor, denosumab, expanded treatment options for MBD, for patients with compromised renal function, in particular. In addition, several other bone-targeting agents, including bone anabolic drugs, are currently in preclinical and early clinical assessment. This review summarizes our up-to-date knowledge on the pathogenesis of MBD and discusses novel state-of-the-art treatment strategies that are likely to enter clinical practice in the near future.

scholarly journals Increasing trends in the prevalence of prior cancer in newly diagnosed lung, stomach, colorectal, breast, cervical, and corpus uterine cancer patients: A population-based study

2021 ◽  
Author(s):  
Akira Sato ◽  
Keisuke Matsubayashi ◽  
Toshitaka Morishima ◽  
Kayo Nakata ◽  
Koji Kawakami ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Research ◽  
Cancer Patients ◽  
Uterine Cancer ◽  
Treatment Options ◽  
Temporal Trends ◽  
Treatment Strategies ◽  
Population Based ◽  
Trend Test ◽  
Newly Diagnosed

Abstract Background: Cancer survivors are frequently excluded from clinical research, resulting in their omission from the development of many cancer treatment strategies. Quantifying the prevalence of prior cancer in newly diagnosed cancer patients can inform research and clinical practice. This study aimed to describe the prevalence, characteristics, and trends of prior cancer in newly diagnosed cancer patients in Japan. Methods: Using Osaka Cancer Registry data, we examined the prevalence, characteristics, and temporal trends of prior cancer in patients who received new diagnoses of lung, stomach, colorectal, female breast, cervical, and corpus uterine cancer between 2004 and 2015. Site-specific prior cancers were examined for a maximum of 15 years before the new cancer was diagnosed. Temporal trends were evaluated using the Cochran-Armitage trend test. Results: Among 275,720 newly diagnosed cancer patients, 21,784 (7.9%) had prior cancer. The prevalence of prior cancer ranged from 3.3% (breast cancer) to 11.1% (lung cancer). In both sexes, the age-adjusted prevalence of prior cancer had increased in recent years (P values for trend < 0.001), especially in newly diagnosed lung cancer patients. The proportion of smoking-related prior cancers exceeded 50% in patients with newly diagnosed lung, stomach, colorectal, breast, and cervical cancer. Conclusions: The prevalence of prior cancer in newly diagnosed cancer patients is relatively high, and has increased in recent years. Our findings suggest that a deeper understanding of the prevalence and characteristics of prior cancer in cancer patients is needed to promote more inclusive clinical research and support the expansion of treatment options.

scholarly journals Up-regulation of Mitotic Nuclear Division-related Genes and Down-regulation of TGF-β-related Genes Correlate with Survival in Malignant Pleural Mesothelioma

2021 ◽  
Author(s):  
Lili Su ◽  
Yonggang Wang ◽  
Daowei Li ◽  
Xingguang Wang ◽  
Bin Liang ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Nuclear Division ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Pleural Mesothelioma ◽  
Related Gene ◽  
Down Regulation

Abstract Malignant pleural mesothelioma (MPM) is a highly aggressive and lethal malignancy; however, its molecular origins remain largely unknown. The purpose of this study was to use transcriptomics to explore the molecular mechanisms of MPM tumorigenesis toward gaining a better understanding of disease development. The transcriptomes from MPM tissues and paired normal pleural tissues were compared to identify significantly differentially expressed genes. These genes were then subject to Gene Ontology analysis to explore pathways that are dysregulated in MPM, and The Cancer Genome Atlas (TCGA) gene expression profile data were analyzed to assess the correlation between the significantly dysregulated pathways and patient survival. Moreover, three independent transcriptomic datasets were used to validate the association between significantly dysregulated genes and the clinical features of MPM. We identified 136 up-regulated and 599 down-regulated genes in MPM tissues as compared to normal pleural tissues. Functional enrichment analysis showed that the up-regulated genes were mainly associated with mitotic nuclear division, whereas the down-regulated genes were mainly associated with transforming growth factor beta (TGF-β) signaling. The 14 most significantly up-regulated mitotic nuclear division-related genes were more likely to be highly expressed in pathological subtypes with higher malignancy, whereas the down-regulated TGF-β pathway-related gene PPARGC1A displayed the opposite trend. In the TCGA dataset, up-regulation of mitotic nuclear division-related genes was associated with a poor prognosis, whereas down-regulation of TGF-β pathway-related genes was associated with a positive prognosis. The down-regulated PPARGC1A were further validated by immunohistochemical analysis. In summary, the correlation between up-regulation of mitotic nuclear division-related genes and down-regulation of the TGF-β pathway-related gene PPARGC1A with overall survival indicates an important role for these genes in MPM development and progression.

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