Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation

Ferrari, Luca; Carugno, Michele; Mensi, Carolina; Pesatori, Angela Cecilia

doi:10.3389/fonc.2020.00445

Cited by 21 publications

(29 citation statements)

References 104 publications

(120 reference statements)

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“…This trial showed a partial response in 1 of 22 patients (64). It is increasing the probability of non-coding RNAs in serum or plasma as circulating MPM biomarkers (15). Downregulated expression of miR-126 in serum from MPM patients was confirmed by several groups, but the discrimination power between MPM patients and healthy controls is not so high (15).…”

Section: Non-coding Rnas Immunotherapy With Icis In Mpmmentioning

confidence: 94%

“…It is increasing the probability of non-coding RNAs in serum or plasma as circulating MPM biomarkers (15). Downregulated expression of miR-126 in serum from MPM patients was confirmed by several groups, but the discrimination power between MPM patients and healthy controls is not so high (15). A combination of circulating biomarkers is expected to overcome the poor sensitivity and specificity of single markers.…”

Section: Non-coding Rnas Immunotherapy With Icis In Mpmmentioning

confidence: 99%

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Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors–Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment

et al. 2020

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Malignant pleural mesothelioma (MPM) is strongly associated with occupational or environmental asbestos exposure and arises from neoplastic transformation of mesothelial cells in the pleural cavity. The only standard initial treatment for unresectable MPM is combination chemotherapy with cisplatin (CDDP) and pemetrexed (PEM). Further, CDDP/PEM is the only approved regimen with evidence of prolonged overall survival (OS), although the median OS for patients treated with this regimen is only 12 months after diagnosis. Thus, the development of new therapeutic strategies has been investigated for approximately 20 years. In contrast to recent advances in personalized lung cancer therapies, diagnostic and prognostic biomarker research has just started in mesothelioma. Epigenetic alterations include DNA methylation, histone modifications, and other chromatin-remodeling events. These processes are involved in numerous cellular processes including differentiation, development, and tumorigenesis. Epigenetic modifications play an important role in gene expression and regulation related to malignant MPM phenotypes and histological subtypes. An immune checkpoint PD-1 inhibitor, nivolumab, was approved as second-line therapy for patients who had failed initial chemotherapy, based on the results of the MERIT study. Various clinical immunotherapy trials are ongoing in patients with advanced MPM. In this review, we describe recent knowledge on epigenetic alterations, which might identify candidate therapeutic targets and immunotherapeutic regimens under development for MPM.

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Section: Non-coding Rnas Immunotherapy With Icis In Mpmmentioning

confidence: 94%

Section: Non-coding Rnas Immunotherapy With Icis In Mpmmentioning

confidence: 99%

Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors–Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment

et al. 2020

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“…Among the epigenetic modifications affecting the genome, DNA methylation, the process by which a methyl group is added to carbon five in the cytosine pyridine ring forming 5-methylcytosine (5 mC) in DNA, is the most studied for the assessment of the potential hazard of fiber-like materials. Mesothelioma, as well other asbestos-related diseases, has been related to epigenetic changes, and the methylation changes of blood markers have been proposed as diagnostic and prognostic markers for mesothelioma [ 61 , 62 , 63 ]. In recent epidemiological studies in asbestos-exposed populations, a decrease in the levels of blood global 5-methylcytosine (5 mC) has been described in both healthy exposed workers and in those with benign asbestos-related disorders, confirming that global methylation could be a useful marker of asbestos exposure but, unfortunately, cannot be used as indicator of asbestos-related disease [ 64 , 65 ].…”

Section: Carbon Nanotubes and The Hallmarks Of Cancermentioning

confidence: 99%

Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System

Barbarino

Giordano

2021

Cancers

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In 2014, the International Agency for Research on Cancer (IARC) classified the first type of carbon nanotubes (CNTs) as possibly carcinogenic to humans, while in the case of other CNTs, it was not possible to ascertain their toxicity due to lack of evidence. Moreover, the physicochemical heterogeneity of this group of substances hamper any generalization on their toxicity. Here, we review the recent relevant toxicity studies produced after the IARC meeting in 2014 on an homogeneous group of CNTs, highlighting the molecular alterations that are relevant for the onset of mesothelioma. Methods: The literature was searched on PubMed and Web of Science for the period 2015–2020, using different combinations keywords. Only data on normal cells of the respiratory system after exposure to fully characterized CNTs for their physico-chemical characteristics were included. Recent studies indicate that CNTs induce a sustained inflammatory response, oxidative stress, fibrosis and histological alterations. The development of mesothelial hyperplasia, mesothelioma, and lungs tumors have been also described in vivo. The data support a strong inflammatory potential of CNTs, similar to that of asbestos, and provide evidence that CNTs exposure led to molecular alterations known to have a key role in mesothelioma onset. These evidences call for an urgent improvement of studies on exposed human populations and adequate systems for monitoring the health of workers exposed to this putative carcinogen.

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“…Some of the epigenetic modifications reported above can be detected in biological fluids, such as plasma, serum, urine, or cerebrospinal fluid. These molecules, reported as "circulating biomarkers", are receiving particular attention with regard to cancer diagnosis for their non-invasive collection method [88]. Moreover, epigenetic alterations have been often found in early-stage patients [24,69], thus representing a promising tool for an early diagnosis.…”

Section: Epigenetic Features As Diagnostic and Prognostic Markers In Mpmmentioning

confidence: 99%

Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations

Lorenzini

Ciarrocchi

Torricelli

2021

JCM

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Malignant pleural mesothelioma (MPM) is a clinical emergency of our time. Being strongly associated with asbestos exposure, incidence of this cancer is ramping up these days in many industrialized countries and it will soon start to increase in many developing areas where the use of this silicate derivate is still largely in use. Deficiency of reliable markers for the early identification of these tumors and the limited efficacy of the currently available therapeutic options are the basis of the impressive mortality rate of MPM. These shortcomings reflect the very poor information available about the molecular basis of this disease. Results of the recently released deep profiling studies point to the epigenome as a central element in MPM development and progression. First, MPM is characterized by a low mutational burden and a highly peculiar set of mutations that hits almost exclusively epigenetic keepers or proteins controlling chromatin organization and function. Furthermore, asbestos does not seem to be associated with a distinctive mutational signature, while the precise mapping of epigenetic changes caused by this carcinogen has been defined, suggesting that alterations in epigenetic features are the driving force in the development of this disease. Last but not least, consistent evidence also indicates that, in the setting of MPM, chromatin rewiring and epigenetic alterations of cancer cells heavily condition the microenvironment, including the immune response. In this review we aim to point to the relevance of the epigenome in MPM and to highlight the dependency of this tumor on chromatin organization and function. We also intend to discuss the opportunity of targeting these mechanisms as potential therapeutic options for MPM.

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Circulating Epigenetic Biomarkers in Malignant Pleural Mesothelioma: State of the Art and critical Evaluation

Cited by 21 publications

References 104 publications

Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors–Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment

Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors–Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment

Assessment of the Carcinogenicity of Carbon Nanotubes in the Respiratory System

Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations

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