Chemical Profiling of Primary Mesothelioma Cultures Defines Subtypes with Different Expression Profiles and Clinical Responses

Abstract

Finding new treatment options for patients with malignant pleural mesothelioma is challenging due to the rarity and heterogeneity of this cancer type. The absence of druggable targets further complicates the development of new therapies. Current treatment options are therefore limited, and prognosis remains poor. We performed drug screening on primary mesothelioma cultures to guide treatment decisions of corresponding patients that were progressive after first- or second-line treatment. We observed a high concordance between results and clinical outcomes. We defined three subgroups responding differently to the anticancer drugs tested. In addition, gene expression profiling yielded distinct signatures that segregated the differently responding subgroups. These genes signatures involved various pathways, most prominently the fibroblast growth factor pathway. Our primary mesothelioma culture system has proved to be suitable to test novel drugs. Chemical profiling of primary mesothelioma cultures allows personalizing treatment for a group of patients with a rare tumor type where clinical trials are notoriously difficult. This personalized treatment strategy is expected to improve the poor prospects of patients with mesothelioma. .

Genomics and Functional Genomics of Malignant Pleural Mesothelioma

“…Correspondingly, the nonresponder primary cultures were found to be sensitive to the FGFR inhibitor, PD-173074. More importantly, in vitro drug responses of primary cultures were predictive of clinical responses to select drugs, suggesting that preliminary culture systems are suitable to identify mechanistic determinants of drug responses, and personalize treatment regimens [ 197 ].…”

Progress in the Management of Malignant Pleural Mesothelioma in 2017

“…To further bridge preclinical and clinical results, the availability of relevant in vitro and in vivo models is crucial. In this respect, the establishment of primary MPM culture systems to test novel drugs 178, 179 as well as of patient-derived xenografts from pleural mesothelioma 180 represented a significant scientific advance in 2017.…”

Trophoblast Glycoprotein is Associated With a Favorable Outcome for Mesothelioma and a Target for Antibody Drug Conjugates

“…Isolating tumor cells from pleural fluid as described generated early passage cell lines NKI04, PV130913, PV180314, PV170614, and PV041214. 26 LnCap cells were cultured in Roswell Park Memorial Institute solution (Life Technologies, Carlsbad, California) with 10% FCS. All cells were maintained at 37 C, 5% CO 2 .…”