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

Laurel M Schunselaar ,
Josine M M F Quispel-Janssen ,
Yongsoo Kim ,
Constantine Alifrangis ,
Wilbert Zwart ,
Paul Baas ,
Jacques Neefjes

Abstract

Purpose: 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.Experimental Design: We performed drug screening on primary mesothelioma cultures to guide treatment decisions of corresponding patients that were progressive after first- or second-line treatment.Results: We observed a high concordance between in vitro 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.Conclusions: 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. Clin Cancer Res; 24(7); 1761-70. ©2017 AACRSee related commentary by John and Chia, p. 1513.

More about this publication

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume 24
Issue nr. 7
Pages 1761-1770
Publication date 01-04-2018

Full text links

Publisher website (DOI) 10.1158/1078-0432.CCR-17-1345
Europe PubMed Central 29066506
Pubmed 29066506

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