Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease 
affecting the mesothelium, commonly associated to asbestos exposure. Therapeutic 
actions are limited due to the late stage at which most patients are diagnosed 
and the intrinsic chemo-resistance of the tumor. The recommended systemic 
therapy for MPM is cisplatin/pemetrexed regimen with a mean overall survival of 
about 12months and a median progression free survival of less than 6months. 
Considering that the incidence of this tumor is expected to increase in the next 
decade and that its prognosis is poor, novel therapeutic approaches are urgently 
needed. For some tumors, such as lung cancer and breast cancer, druggable 
oncogenic alterations have been identified and targeted therapy is an important 
option for these patients. For MPM, clinical guidelines do not recommend 
biological targeted therapy, mainly because of poor target definition or 
inappropriate trial design. Further studies are required for a full 
comprehension of the molecular pathogenesis of MPM and for the development of 
new target agents. This review updates pre-clinical and clinical data on the 
efficacy of targeted therapy and immune checkpoint inhibition in the treatment 
of mesothelioma. Finally, future perspectives in this deadly disease are also 
discussed.