title: Ex VivoExplant Cultures of Non-Small Cell Lung Carcinoma Enable Evaluation of Primary Tumor Responses to Anticancer Therapy.
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 optimizedex vivoexplant 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 respondingex vivoNotably, 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 andTP53mutation 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 tumorsex vivo, thereby enabling preclinical testing of novel drugs and helping stratify patients using biomarker evaluation.Cancer Res; 77(8); 2029-39. ©2017 AACR.
authors.affiliation: Department of Cancer Studies, University of Leicester, Leicester, United Kingdom.
authors.forename: Ellie
authors.initials: E
authors.lastname: Karekla
authors.affiliation: Department of Cancer Studies, University of Leicester, Leicester, United Kingdom.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Liao
authors.affiliation: Centre for Analytical Science, Department of Chemistry, Loughborough University, Loughborough, Leicestershire, United Kingdom.
authors.forename: Barry
authors.initials: B
authors.lastname: Sharp
authors.affiliation: Centre for Analytical Science, Department of Chemistry, Loughborough University, Loughborough, Leicestershire, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Pugh
authors.affiliation: Centre for Analytical Science, Department of Chemistry, Loughborough University, Loughborough, Leicestershire, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Reid
authors.affiliation: Department of Cancer Studies, University of Leicester, Leicester, United Kingdom.|MRC Toxicology Unit, Leicester, United Kingdom.
authors.forename: John Le
authors.initials: JL
authors.lastname: Quesne
authors.affiliation: Department of Cancer Studies, University of Leicester, Leicester, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Moore
authors.affiliation: Department of Cancer Studies, University of Leicester, Leicester, United Kingdom. cap8@le.ac.uk mm21@le.ac.uk.
authors.forename: Catrin
authors.initials: C
authors.lastname: Pritchard
authors.affiliation: MRC Toxicology Unit, Leicester, United Kingdom. cap8@le.ac.uk mm21@le.ac.uk.
authors.forename: Marion
authors.initials: M
authors.lastname: MacFarlane
authors.affiliation: Department of Cancer Studies, University of Leicester, Leicester, United Kingdom.
authors.forename: James Howard
authors.initials: JH
authors.lastname: Pringle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D046509:Tissue Culture Techniques / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin