Roberta Affatato1, Paolo Mendogni2, Alessandro Del Gobbo3, Stefano Ferrero3,4, Francesca Ricci1, Massimo Broggini1, Lorenzo Rosso2. 1. Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy. 2. Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy. 3. Division of Pathology, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy. 4. Department of Biomedical Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy.
Abstract
BACKGROUND: Malignant pleural mesothelioma (MPM) is a very aggressive tumor originating from mesothelial cells. Although several etiological factors were reported to contribute to MPM onset, environmental exposure to asbestos is certainly a major risk factor. The latency between asbestos (or asbestos-like fibers) exposure and MPM onset is very long. MPM continues to be a tumor with poor prognosis despite the introduction of new therapies including immunotherapy. One of the major problems is the low number of preclinical models able to recapitulate the features of human tumors. This impacts the possible discovery of new treatments and combinations. METHODS: In this work, we aimed to generate patient-derived xenografts (PDXs) from MPM patients covering the three major histotypes (epithelioid, sarcomatoid, and mixed) occurring in the clinic. To do this, we obtained fresh tumors from biopsies or pleurectomies, and samples were subcutaneously implanted in immunodeficient mice within 24 h. RESULTS: We successfully isolated different PDXs and particularly concentrated our efforts on three covering the three histotypes. The tumors that grew in mice compared well histologically with the tumors of origin, and showed stable growth in mice and a low response to cisplatin, as was observed in the clinic. CONCLUSIONS: These models are helpful in testing new drugs and combinations that, if successful, could rapidly translate to the clinical setting.
BACKGROUND:Malignant pleural mesothelioma (MPM) is a very aggressive tumor originating from mesothelial cells. Although several etiological factors were reported to contribute to MPM onset, environmental exposure to asbestos is certainly a major risk factor. The latency between asbestos (or asbestos-like fibers) exposure and MPM onset is very long. MPM continues to be a tumor with poor prognosis despite the introduction of new therapies including immunotherapy. One of the major problems is the low number of preclinical models able to recapitulate the features of humantumors. This impacts the possible discovery of new treatments and combinations. METHODS: In this work, we aimed to generate patient-derived xenografts (PDXs) from MPM patients covering the three major histotypes (epithelioid, sarcomatoid, and mixed) occurring in the clinic. To do this, we obtained fresh tumors from biopsies or pleurectomies, and samples were subcutaneously implanted in immunodeficientmice within 24 h. RESULTS: We successfully isolated different PDXs and particularly concentrated our efforts on three covering the three histotypes. The tumors that grew in mice compared well histologically with the tumors of origin, and showed stable growth in mice and a low response to cisplatin, as was observed in the clinic. CONCLUSIONS: These models are helpful in testing new drugs and combinations that, if successful, could rapidly translate to the clinical setting.
Entities:
Keywords:
3D cultures; cell lines; in vivo models; malignant pleural mesothelioma; patient-derived xenografts
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