Ex vivo explant cultures of non–small cell lung carcinoma enable evaluation of primary tumor responses to anticancer therapy

Karekla, E., Liao, W.-J., Sharp, B., Pugh, J., Reid, H., Le Quesne, J., Moore, D., Pritchard, C., MacFarlane, M. and Pringle, J. H. (2017) Ex vivo explant cultures of non–small cell lung carcinoma enable evaluation of primary tumor responses to anticancer therapy. Cancer Research, 77(8), pp. 2029-2039. (doi: 10.1158/0008-5472.CAN-16-1121) (PMID:28202521)

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Abstract

To improve treatment outcomes in non–small cell lung cancer (NSCLC), preclinical models that can better predict individual patient response to novel therapies are urgently needed. Using freshly resected tumor tissue, we describe an optimized ex vivo explant culture model that enables concurrent evaluation of NSCLC response to therapy while maintaining the tumor microenvironment. We found that approximately 70% of primary NSCLC specimens were amenable to explant culture with tissue integrity intact for up to 72 hours. Variations in cisplatin sensitivity were noted with approximately 50% of cases responding ex vivo. Notably, explant responses to cisplatin correlated significantly with patient survival (P = 0.006) irrespective of tumor stage. In explant tissue, cisplatin-resistant tumors excluded platinum ions from tumor areas in contrast to cisplatin-sensitive tumors. Intact TP53 did not predict cisplatin sensitivity, but a positive correlation was observed between cisplatin sensitivity and TP53 mutation status (P = 0.003). Treatment of NSCLC explants with the targeted agent TRAIL revealed differential sensitivity with the majority of tumors resistant to single-agent or cisplatin combination therapy. Overall, our results validated a rapid, reproducible, and low-cost platform for assessing drug responses in patient tumors ex vivo, thereby enabling preclinical testing of novel drugs and helping stratify patients using biomarker evaluation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Le Quesne, Professor John
Authors: Karekla, E., Liao, W.-J., Sharp, B., Pugh, J., Reid, H., Le Quesne, J., Moore, D., Pritchard, C., MacFarlane, M., and Pringle, J. H.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cancer Research
Publisher:American Association for Cancer Research
ISSN:0008-5472
ISSN (Online):1538-7445
Published Online:15 February 2017
Copyright Holders:Copyright © 2017 American Association for Cancer Research
First Published:First published in Cancer Research 77(8): 2029-2039
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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