The resistance related to targeted therapy in malignant pleural mesothelioma: Why has not the target been hit yet?
Malignant pleural mesothelioma (MPM) is an aggressive tumor of the pleura with a poor prognosis. The most active first-line regimens are platinum compounds and pemetrexed. There is no standard second-line treatment in MPM. Advances in the understanding of tumor molecular biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. Unfortunately none of the explored targeted treatments can currently be recommended as routine treatment in MPM. We reviewed the biological pathways involved in MPM, the clinical trials about targeted therapy, and possible related mechanisms of resistance. We suggest that specific genetic markers are needed as targets of selective therapy. By this way the selection of patients based on the molecular profile may facilitate a therapeutic strategy that allows the use of the most appropriate drug for each patient.
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Giuseppe
G
Bronte
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Lorena
L
Incorvaia
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Sergio
S
Rizzo
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Francesco
F
Passiglia
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Antonio
A
Galvano
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Fabio
F
Rizzo
Phase I- Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium.
Christian
C
Rolfo
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Daniele
D
Fanale
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Angela
A
Listì
Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti, Italy.
Clara
C
Natoli
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
Viviana
V
Bazan
Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy. Electronic address: antonio.russo@usa.net.
Antonio
A
Russo
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics; D000086002:Mesothelioma, Malignant; D058990:Molecular Targeted Therapy; D009154:Mutation; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents
Mesothelioma; Pleura; Resistance; Targeted therapy