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|Title:||Ex Vivo Explant Cultures of Non-Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy.|
Le Quesne, John
Pringle, James Howard
|Publisher:||American Association for Cancer Research|
|Citation:||Cancer Research, 2017, 77 (8), pp. 2029-2039|
|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.|
|Rights:||Copyright © 2017, American Association for Cancer Research. Deposited with reference to the publisher’s open access archiving policy.|
|Description:||Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).|
The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
|Appears in Collections:||Published Articles, Dept. of Cancer Studies and Molecular Medicine|
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|Karekla et al.pdf||Post-review (final submitted author manuscript)||8.98 MB||Adobe PDF||View/Open|
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