Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?

Author:

Borea Federica12,Franczak Marika A.23ORCID,Garcia Maria4,Perrino Matteo5,Cordua Nadia5,Smolenski Ryszard T.3ORCID,Peters Godefridus J.23ORCID,Dziadziuszko Rafal6,Santoro Armando15,Zucali Paolo A.15ORCID,Giovannetti Elisa27ORCID

Affiliation:

1. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20090 Milan, Italy

2. Department of Medical Oncology, Amsterdam University Medical Centers, Location VUmc, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands

3. Department of Biochemistry, Medical University of Gdansk, 80-210 Gdańsk, Poland

4. Faculty of Experimental Science, Universidad Francisco de Vitoria, 28223 Madrid, Spain

5. IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, Rozzano, 20089 Milan, Italy

6. Department of Oncology and Radiotherapy and Early Phase Clinical Trials Centre, Medical University of Gdansk, 80-210 Gdańsk, Poland

7. Fondazione Pisana per la Scienza, 56017 Pisa, Italy

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.

Funder

National Science Center of Poland

Mesothelioma Applied Research Foundation, US, and by Italian Association for the Study of Cancer

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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