TY - JOUR
T1 - Chemical profiling of primary mesothelioma cultures defines subtypes with different expression profiles and clinical responses
AU - Schunselaar, Laurel M.
AU - Quispel-Janssen, Josine M.M.F.
AU - Kim, Yongsoo
AU - Alifrangis, Constantine
AU - Zwart, Wilbert
AU - Baas, Paul
AU - Neefjes, Jacques
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046376274&partnerID=8YFLogxK
U2 - https://doi.org/10.1158/1078-0432.CCR-17-1345
DO - https://doi.org/10.1158/1078-0432.CCR-17-1345
M3 - Article
C2 - 29066506
SN - 1078-0432
VL - 24
SP - 1761
EP - 1770
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -