Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future

Abstract

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CART cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and ongoing clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.

PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

“…1 MPM is associated with asbestos exposure, which is responsible for 80% of the diagnosed cases, 2 and is an aggressive cancer with a grim prognosis. 1 The median survival period of patients with MPM is 8–14 months 3 and the 5-year overall survival (OS) rate is 8.5%. 4 For localized disease of MPM, the mainstay therapeutic strategies are surgical resection with or without radiotherapy and/or chemotherapy, whereas for patients with unresectable disease, multimodality therapy including radiotherapy and chemotherapy is usually selected.…”

Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells

“…Malignant pleural mesothelioma (MPM) is a rare malignancy originated from pleura mesothelium, frequently related to asbestos fiber, whose incidence in Europe is expected to peak approximately around 2025 [ 1 ]. Only few patients are eligible for the trimodality therapy, including surgery, chemotherapy and radiotherapy, while for the majority of patients the prognosis remains poor and the median survival is around 8–14 months [ 2 ]. Genomic analysis of mesothelioma has revealed inactivation of tumor suppressor pathways rather than activation of oncogenes.…”

Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin

“…Additional anti-angiogenic drugs, such as cediranib (anti-VEGF receptor and platelet-derived growth factor (PDGF) receptor inhibitor), nintedanib (anti-VEGFR, PDGFR, and fibroblast growth factor (FGF) receptor inhibitor), axitinib (anti-VEGFR inhibitor), and soferanib (multi-target inhibitor of VEGFR1/2/3, FGFR-1, PDGFR-β, and RAF/cKit pathway) have also been examined for additive effects; however, they have only limited effects. Recently, the effects of immune checkpoint inhibitors (ICIs), including anti-CTLA-4 antibodies and anti-PD-1/PD-L1 antibodies, on various malignant tumors have been reported [36][37][38]. A combination of ICIs and chemotherapy has been evaluated in several clinical trials.…”