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Emerging Therapies for Malignant Mesothelioma
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Emerging Therapies for Malignant Mesothelioma

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 8058

Special Issue Editors

Prof. Dr. Ioannis Kalomenidis

E-Mail Website
Guest Editor
1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 10675 Athens, Greece
Interests: mesothelioma; malignant pleural effusion; tumor immunology; tumor-host interactions; pleural diseases
Dr. Magkouta Sophia

E-Mail Website
Guest Editor
“Marianthi Simou Laboratory”, 1st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, School of Medicine, Evangelismos Hospital, 10675 Athens, Greece
Interests: mesothelioma; malignant pleural effusion; tumor immunology; tumor–host interactions

Special Issue Information

Dear Colleagues,

International Journal of Molecular Sciences  (IF 5.923) is preparing a Special Issue entitled "Emerging Therapies for Malignant Mesothelioma". Among malignancies, mesothelioma poses unique challenges in the field of therapeutics, since it is highly resistant to current treatment manipulations and therefore always fatal. Albeit several early clinical findings have been promising, many important issues remain unresolved such as the ‘ideal’ drug or drug combinations, proper selection of patients most likely to respond. Albeit we know that interactions among tumor cells and the host (inflammatory populations, tumor endothelium or the stroma) is crucial to support drug resistance and mesothelioma progression, mesothelioma tumor microenvironment is still poorly understood. More insights on the cellular and molecular mechanisms underlying tumor cell survival and resistance are therefore vital for the design of more effective therapeutic strategies.

This special issue will be dedicated to publish original work and reviews on unveiling new targets, predictive biomarkers, therapeutic schemes-manipulations, tools are therefore highly encouraged. Submitted studies could include experimental (preclinical-organoids/animal studies), clinical or computational (for example: discovery of biomarkers upon machine learning) results related to mesothelioma.

Sincerely,
Prof. Dr. Ioannis Kalomenidis
Dr. Magkouta Sophia
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pleural mesothelioma
  • immunotherapy
  • combination therapy
  • clinical trial
  • preclinical studies
  • pleural fluid
  • tumor microenvironment
  • adjuvant therapy
  • radiation therapy
  • cancer vaccines
  • nanotechnology
  • biomarkers

Published Papers (4 papers)

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Research

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11 pages, 2317 KiB  
Article
Cancer-Associated Fibroblasts Regulate Kinase Activity in Mesothelioma Cell Lines via Paracrine Signaling and Thereby Dictate Cell Faith and Behavior
by Alexander Mathilakathu, Michael Wessolly, Elena Mairinger, Hendrik Uebner, Daniel Kreidt, Luka Brcic, Julia Steinborn, Kristina Greimelmaier, Jeremias Wohlschlaeger, Kurt Werner Schmid, Fabian D. Mairinger and Sabrina Borchert
Int. J. Mol. Sci. 2022, 23(6), 3278; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063278 - 18 Mar 2022
Cited by 4 | Viewed by 1720
Abstract
Background: Malignant pleural mesothelioma (MPM) has an infaust prognosis due to resistance to systemic treatment with platin-analoga. MPM cells modulate the immune response to their benefit. They release proinflammatory cytokines, such as TGF-ß, awakening resting fibrocytes that switch their phenotype into activated fibroblasts. [...] Read more.
Background: Malignant pleural mesothelioma (MPM) has an infaust prognosis due to resistance to systemic treatment with platin-analoga. MPM cells modulate the immune response to their benefit. They release proinflammatory cytokines, such as TGF-ß, awakening resting fibrocytes that switch their phenotype into activated fibroblasts. Signaling interactions between cancer cells and cancer-associated fibroblasts (CAFs) play an integral part in tumor progression. This study aimed to investigate the role CAFs play in MPM progression, analyzing the impact this complex, symbiotic interaction has on kinase-related cell signaling in vitro. Methods: We simulated paracrine signaling in vitro by treating MPM cell lines with conditioned medium (CM) from fibroblasts (FB) and vice versa. NCI-H2052, MSTO-211H, and NCI-H2452 cell lines representing the three mayor MPM subtypes, while embryonal myofibroblast cell lines, IMR-90 and MRC-5, provide a CAFs-like phenotype. Subsequently, differences in proliferation rates, migratory behavior, apoptosis, necrosis, and viability were used as covariates for data analysis. Kinase activity of treated samples and corresponding controls were then analyzed using the PamStation12 platform (PamGene); Results: Treatment with myofibroblast-derived CM revealed significant changes in phosphorylation patterns in MPM cell lines. The observed effect differs strongly between the analyzed MPM cell lines and depends on the origin of CM. Overall, a much stronger effect was observed using CM derived from IMR-90 than MRC-5. The phosphorylation changes mainly affected the MAPK signaling pathway.; Conclusions: The factors secreted by myofibroblasts in fibroblasts CM significantly influence the phosphorylation of kinases, mainly affecting the MAPK signaling cascade in tested MPM cell lines. Our in vitro results indicate promising therapeutic effects by the use of MEK or ERK inhibitors and might have synergistic effects in combination with cisplatin-based treatment, improving clinical outcomes for MPM patients. Full article
(This article belongs to the Special Issue Emerging Therapies for Malignant Mesothelioma)
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Review

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21 pages, 857 KiB  
Review
The Genes–Stemness–Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints
by Giulia M. Stella, Caterina Marchiò, Elia Bari, Ilaria Ferrarotti, Francesco R. Bertuccio, Antonella Di Gennaro, David Michael Abbott, Paola Putignano, Ilaria Campo, Maria Luisa Torre and Angelo G. Corsico
Int. J. Mol. Sci. 2023, 24(4), 3496; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043496 - 09 Feb 2023
Viewed by 1477
Abstract
MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional [...] Read more.
MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional crosstalk between neoplastic cells and matrix components, among which one main area of focus is hypoxia. Here we discuss the novel therapeutic strategies focused on the exploitation of MPM genetic asset and its interconnection with the surrounding hypoxic microenvironment as well as transcript products and microvesicles representing both an insight into the pathogenesis and promising actionable targets. Full article
(This article belongs to the Special Issue Emerging Therapies for Malignant Mesothelioma)
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14 pages, 721 KiB  
Review
The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma
by Juuso Paajanen, Raphael Bueno and Assunta De Rienzo
Int. J. Mol. Sci. 2022, 23(21), 13422; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113422 - 03 Nov 2022
Cited by 3 | Viewed by 1662
Abstract
Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20–40 years from the time of asbestos exposure [...] Read more.
Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20–40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets. Full article
(This article belongs to the Special Issue Emerging Therapies for Malignant Mesothelioma)
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13 pages, 413 KiB  
Review
Novel and Future Treatment Options in Mesothelioma: A Systematic Review
by Danijela Štrbac and Vita Dolžan
Int. J. Mol. Sci. 2022, 23(4), 1975; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23041975 - 10 Feb 2022
Cited by 9 | Viewed by 2529
Abstract
Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy [...] Read more.
Mesothelioma is a rare tumor, frequently associated with asbestos exposure, arising from pleura and peritoneum. Traditionally, diagnosis and treatment have been difficult in a clinical setting. The treatment is based on a trimodal approach involving surgery, chemotherapy, and radiotherapy. The introduction of chemotherapy improved the overall survival. However, the regimen of pemetrexed/cisplatin doublet has not been changed as a standard treatment since 2004. Novel combinations of ipilimumab and nivolumab have only been approved for clinical use in late 2020. The aim of this review was to systematically summarize findings on novel treatment options in mesothelioma. We searched available medical databases online, such as PubMed and Clinicaltrials.gov, to systematically review the literature on novel approaches in immunotherapy, vaccines, and Chimeric Antigen Receptor (CAR)-T cell therapy in mesothelioma. We manually screened 1127 articles on PubMed and 450 trials on ClinicalTrials.gov, and 24 papers and 12 clinical trials published in the last ten years were included in this review. Immunotherapy that was swiftly introduced to treat other thoracic malignancies was slow to reach desirable survival endpoints in mesothelioma, possibly due to limited patient numbers. Novel treatment approaches, such as CAR-T cell therapy, are being investigated. As the incidence of mesothelioma is still rising globally, novel treatment options based on a better understanding of the tumor microenvironment and the genetic drivers that modulate it are needed to support future precision-based therapies. Full article
(This article belongs to the Special Issue Emerging Therapies for Malignant Mesothelioma)
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