Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients

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.

The Collagen Receptor uPARAP in Malignant Mesothelioma: A Potential Diagnostic Marker and Therapeutic Target

“…Therefore, the actual ADC format used in this work should not be seen as a proposed drug candidate for MM but rather a tool to facilitate the proof of concept. For further studies along this line, optimized ADC candidates will have to be studied in refined MM mouse models in vivo, preferably including patient-derived xenograft models [ 34 ].…”

Management of Pleural Effusion Secondary to Malignant Mesothelioma

“…An interesting issue is the high potential of patient-derived xenografts (PDXs) in testing new therapies against MPM, as reported by Affatato et al [ 17 ].…”

A Novel PDX Modeling Strategy and Its Application in Metabolomics Study for Malignant Pleural Mesothelioma

“…Lack of specimens is the forefront obstacle in MPM research in China, even to the whole globe. Two studies suggested that the patient-derived xenograft (PDX) model, which implants tumor tissue from a patient into recipient mice, is suitable for testing both anti-cancer therapies and the biological functions of genes or proteins in MM (7,8). Compared to cell line-derived xenograft, PDX model better simulates clinical samples for it greatly reserves heterogeneity of the primary tumor (8).…”