**1. Introduction**

Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis. MPM is strongly associated with past exposure to asbestos [1]. Radical surgeries, such as an extrapleural pneumonectomy or pleural decortication, have been performed for treating patients with MPM previously, but favorable results have been observed in only a limited number of patients [2, 3]. Most patients that present with advanced, non-resectable MPM at diagnosis are candidates for systemic treatments. However, systemic chemotherapy can only be administered to patients with good performance status (PS) [4].

In 2003, Vogelzang et al. reported that the combination of pemetrexed and cisplatin (pemetrexed/cisplatin) improved the response rate (RR), progression-free survival (PFS), and overall survival (OS), compared to cisplatin alone [5]. Since then, systemic chemotherapy with platinum and pemetrexed combination has been considered standard therapy for advanced MPM. However, even with this treatment, the PFS and OS have been estimated at 5.7 months and 12.1 months, respectively [5, 6]. A second-line treatment has not been established. According to the US Surveillance, Epidemiology, and End Results Medicare investigation, the most common second-line treatments are pemetrexed-based retreatment or gemcitabine [6].

There is strong evidence that angiogenesis is an important determinant in the development and progression of MPM. There are two main targets for inhibiting angiogenesis. One is the potent mitogen for endothelial cells, vascular endothelial growth factor (VEGF), which transduces signals by binding to two receptors, VEGF receptors −1 and 2. The other is platelet-derived growth factor (PDGF), which functions as an autocrine growth stimulator in the pathogenesis of MPM [7, 8]. With the introduction of angiogenesis inhibitors, several clinical studies have investigated treatments for MPM.

An alternative approach is to target the complex interaction between cancer and host immunity: cancer cells can acquire the ability to evade the host immune system, which curtails their growth [9, 10]. Cancer cells can also actively subvert the immunosuppressive function of T cells and immune checkpoint molecules, such as cytotoxic T lymphocyte antigen (CTLA)-4, programmed cell death (PD)-1, and PD-ligand (PD-L)-1. In recent years, immune checkpoint inhibitors (ICIs) have shown remarkable results in treating multiple types of neoplasms. The etiology and pathogenesis of MPM are mostly attributed to the generation of an immune microenvironment favorable to tumor growth, caused by asbestos-induced damage [11]. There is evidence that ICIs might play an important role in the treatment of MPM; in fact, some encouraging results have emerged in recent years.

Here, we discuss the results of recent trials on systemic therapies against MPM, with a focus on anti-angiogenic inhibitors and ICIs.
