Mesothelioma: Scientific clues for prevention, diagnosis, and therapy

Abstract

Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. The global mesothelioma incidence and mortality rates are unknown, because data are not available from developing countries that continue to use large amounts of asbestos. The incidence rate of mesothelioma has decreased in Australia, the United States, and Western Europe, where the use of asbestos was banned or strictly regulated in the 1970s and 1980s, demonstrating the value of these preventive measures. However, in these same countries, the overall number of deaths from mesothelioma has not decreased as the size of the population and the percentage of old people have increased. Moreover, hotspots of mesothelioma may occur when carcinogenic fibers that are present in the environment are disturbed as rural areas are being developed. Novel immunohistochemical and molecular markers have improved the accuracy of diagnosis; however, about 14% (high-resource countries) to 50% (developing countries) of mesothelioma diagnoses are incorrect, resulting in inadequate treatment and complicating epidemiological studies. The discovery that germline BRCA1-asssociated protein 1 (BAP1) mutations cause mesothelioma and other cancers (BAP1 cancer syndrome) elucidated some of the key pathogenic mechanisms, and treatments targeting these molecular mechanisms and/or modulating the immune response are being tested. The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment. CA Cancer J Clin 2019;69:402-429.

Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma

“…This is mainly because of the extremely small patient population, and mostly exploratory-type trials. 4 However, favorable responses and survival data could be observed across the studies, which are better than historical data. Considering the current limitations of treatment options in the salvage setting, ICI is now a potential rational and medically useful option for patients with unresectable, relapsed MPM, in the absence of any contraindications.…”

“…biomarker in the ICI treatment of MPM Some sensitive and specific immunohistochemistry markers including calretinin and WT1 are used for diagnosing mesothelioma. 4 However, markers for treatment efficiency have not been established. Generally, PD-L1 expression level is used as the representative maker for predicting the efficacy of ICIs.…”

“…It could be because tumors are heterogeneous in nature. 4 It could be partially attributed to the antibodies used; SP-263 is the most commonly used antibody, [30][31][32] and the others include clones E1L3N and 28-8. 33 Furthermore, the histological subtype influences its frequency; PD-L1 expression is higher in non-epithelial mesotheliomas.…”

Detection of Circulating Tumor Cells (CTCs) in Malignant Pleural Mesothelioma (MPM) with the “Universal” CTC-Chip and An Anti-Podoplanin Antibody NZ-1.2

“…In the current study, we did not validate whether cells captured on the NZ1.2-chip were true MPM cells. We have just developed immunostaining of cells captured on the CTC-chip, and will examine loss of nuclear BAP1 expression, which is a useful marker in discrimination between MPM cells and non-malignant mesothelial cells [39].…”

Data mining analysis of the PP2A cell cycle axis in mesothelioma patients

“…Other possible regions affected by this disease are the peritoneum, the pericardium and the tunica of testis and ovary (Bridda, Padoan, Mencarelli, & Frego, 2007). Although rare, with around 3,000 new patients diagnosed each year alone in the United States (Sun, Vaynblat, & Pass, 2017), it is considered a very aggressive and deadly form of cancer (Carbone et al, 2019).…”