A PRECLINICAL INVESTIGATIVE PLATFORM SETUP, AS A TOOL FOR EVALUATING THE EFFICACY OF CETUXIMAB IN ADDITION TO THE STANDARD HUMAN MALIGNANT MESOTHELIOMA CHEMOTHERAPY PROTOCOL.

Mesothelioma is a malignant tumour that arises from mesothelial cells lining the serosal cavities; in most cases it originates in the pleura and in very few cases in the peritoneum; other sites of origin (pericardium and tunica vaginalis of the testis) are extremely rare. The tumour itself is rare with regard to spontaneous occurrence, however it is universally recognized that exposure to asbestos fibres is harmful to human health, since as well as causing an occupational illness known for many years, asbestosis, it also causes malignant pleural and peritoneal mesothelioma as well pulmonary carcinoma, as proven in many epidemiological studies published since the early 1960s. The purposes of the overall PhD program were on the one hand 1) to set up a preclinical investigative platform screening the efficacy of anticancer drugs in human malignant mesothelioma cell lines, based on the integration of data from in vitro and in vivo activities, and on the other hand 2) to adopt this platform investigating the potential benefit of an anticancer monoclonal antibody (cetuximab) in the treatment of human malignant mesothelioma, both as single agent or in adjunct to the standard first line chemotherapy protocol with folate antimetabolite (pemetrexed) and platinum (cisplatin) compounds. At the end of the entire PhD program, it is important to acknowledge the value of having set up a preclinical diagnostic platform to use in screening molecules potentially effective against tumours (i.e. human malignant mesothelioma) strictly connected with the possibility of carrying out experimental preclinical investigations based on a step-wise approach, with a well-defined rationale that brings together the information obtained at different times, from early studies that can be conducted quickly and tend to be less costly in less complex cell systems, to studies in more complex animal models, with consequent time-saving and use of fewer animals.