Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?

Abstract

Malignant Pleural Mesothelioma (MPM) is a rare neoplasm that is typically diagnosed in a locally advanced stage, making it not eligible for radical surgery and requiring systemic treatment. Chemotherapy with platinum compounds and pemetrexed has been the only approved standard of care for approximately 20 years, without any relevant therapeutic advance until the introduction of immune checkpoint inhibitors. Nevertheless, the prognosis remains poor, with an average survival of only 18 months. Thanks to a better understanding of the molecular mechanisms underlying tumor biology, targeted therapy has become an essential therapeutic option in several solid malignancies. Unfortunately, most of the clinical trials evaluating potentially targeted drugs for MPM have failed. This review aims to present the main findings of the most promising targeted therapies in MPM, and to explore possible reasons leading to treatments failures. The ultimate goal is to determine whether there is still a place for continued preclinical/clinical research in this area.

Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma

“…In addition, soluble MSLN is a specific biomarker of MPM in asbestos-exposed subjects ( 43 ), and the diagnostic and prognostic value of MSLN in early MPM was investigated previously ( 19 , 44 , 45 ). A potential therapeutic assay using monoclonal antibodies targeting different MSLN epitopes covering the proximal membrane regions could result in effective antibody-dependent cell-mediated cytotoxicity ( 46 ). Among them, the clinical trials with SS1P, an immunotoxin that contained a murine anti-mesothelin antibody and a portion of Pseudomonas exotoxin, showed its clinical effectivity hampered due to the occurrence of neutralizing anti-drug antibodies (ADAs) ( 47 , 48 ).…”

Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack

“…These drugs reshaped the treatment landscape of non-small cell lung cancer [9], melanoma [10] and cholangiocarcinoma [11], to cite a few. To date, no such revolution has occurred in mesothelioma [12].…”