bims-mesote 2022-05-01 papers

Issue of 2022‒05‒01
three papers selected by
Laura Mannarino
Humanitas Research

Zhongguo Fei Ai Za Zhi. 2022 Apr 20. 25(4): 259-265

[Advances in Immunotherapy for Malignant Pleural Mesothelioma].

Patients with malignant pleural mesothelioma (MPM) usually present with poor prognosis and short survival period, and there has been a lack of effective treatment options for a long time. Chemotherapy has limited improvement in the clinical outcome of advanced patients (the median survival is less than one year), and it is difficult to find suitable targets for targeted therapy. Recent in-depth research on immunotherapy has changed the treatment pattern of MPM. Especially, the dual immunotherapy regimen significantly improved the survival outcome of patients across subgroups and prolonged the survival time of MPM patients. Therefore, it has been approved for unresectable MPM as first-line treatment for patients. The exploration of other mono or combo immunotherapy regimens in the first and second-line settings of MPM is also underway. How to identify the best beneficial population of each regimen through predictive biomarkers is also a hot spot for researchers. This article will focus on the most up-to-date progress of MPM epidemiology, histological characteristics, pathogenesis, treatment patterns and the advances of immunotherapy in the disease. .

Keywords: Biomarkers; Combination therapy; Immune checkpoint inhibitors; Immunotherapy; Malignant pleural mesothelioma

DOI: https://doi.org/10.3779/j.issn.1009-3419.2022.101.17

J Thorac Oncol. 2022 Apr 21. pii: S1556-0864(22)00192-7. [Epub ahead of print]

Medical and surgical care of mesothelioma patients and their relatives carrying germline BAP1 mutations.

Michele Carbone, Harvey I Pass, Guntulu Ak, H Richard Alexander, Paul Baas, Francine Baumann, Andrew M Blakely, Raphael Bueno, Aleksandra Bzura, Giuseppe Cardillo, Jane E Churpek, Irma Dianzani, Assunta De Rienzo, Mitsuru Emi, Salih Emri, Emanuela Felley-Bosco, Dean A Fennell, Raja M Flores, Federica Grosso, Nicholas K Hayward, Mary Hesdorffer, Chuong D Hoang, Peter A Johansson, Hedy L Kindler, Muaiad Kittaneh, Thomas Krausz, Aaron Mansfield, Muzaffer Metintas, Michael Minaai, Luciano Mutti, Maartje Nielsen, Kenneth O'Byrne, Isabelle Opitz, Sandra Pastorino, Francesca Pentimalli, Marc de Perrot, Antonia Pritchard, Robert Taylor Ripley, Bruce Robinson, Valerie Rusch, Emanuela Taioli, Yasutaka Takinishi, Mika Tanji, Anne S Tsao, A Murat Tuncer, Sebastian Walpole, Andrea Wolf, Haining Yang, Yoshie Yoshikawa, Alicia Zolodnick, David S Schrump, Raffit Hassan.

The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma; less frequently breast cancer, several types of skin carcinomas and other tumor types. Mesotheliomas in these patients are significantly less aggressive and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, significant medical, social and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life and is also cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges and our recommendations of how to best care for these patients and their family members, as well as the potential economic and psychosocial impact.

Keywords: BAP1; Mesothelioma; asbestos; cancer genetics; genetic therapy; germline mutations; tumor predisposition syndromes

DOI: https://doi.org/10.1016/j.jtho.2022.03.014

Virchows Arch. 2022 Apr 24.

Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition.

Francesca Napoli, Ida Rapa, Stefania Izzo, Angelica Rigutto, Roberta Libener, Chiara Riganti, Paolo Bironzo, Riccardo Taulli, Mauro Papotti, Marco Volante, Giorgio Scagliotti, Luisella Righi.

The standard front-line treatment for pleural mesothelioma (PM) is pemetrexed-based chemotherapy, whose major target is thymidylate synthase (TS). In several cancer models, miR-215 and miR-375 have been shown to target TS, while information on these miRNAs in PM are still limited although suggest their role in epithelial to mesenchymal transition. Seventy-one consecutive PM tissues (4 biphasic, 7 sarcomatoid, and 60 epithelioid types) and 16 commercial and patient-derived PM cell lines were screened for TS, miR-215, and miR-375 expression. REN and 570B cells were selected for miR-215 and miR-375 transient transfections to test TS modulation. ZEB1 protein expression in tumor samples was also tested. Moreover, genetic profile was investigated by means of BAP1 and p53 immunohistochemistry. Expression of both miR-215 and miR-375 was significantly higher in epithelioid histotype. Furthermore, inverse correlation between TS protein and both miR-215 and miR-375 expression was found. Efficiently transfected REN and 570B cell lines overexpressing miR-215 and miR-375 showed decreased TS protein levels. Epithelioid PM with a mesenchymal component highlighted by reticulin stain showed significantly higher TS and ZEB1 protein and lower miRNA expression. A better survival was recorded for BAP1 lost/TS low cases. Our data indicate that miR-215 and miR-375 are involved in TS regulation as well as in epithelial-to-mesenchymal transition in PM.

Keywords: Cell lines; Epithelial to mesenchymal transition; Micro-RNA; Pleural mesothelioma; Thymidylate synthase; Tissue expression

DOI: https://doi.org/10.1007/s00428-022-03321-8