دورية أكاديمية
Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data.
| العنوان: | Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data. |
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| المؤلفون: | Buhl, I.K., Gerster, S., Delorenzi, M., Jensen, T., Jensen, P.B., Bosman, F., Tejpar, S., Roth, A., Brunner, N., Hansen, A., Knudsen, S. |
| المصدر: | PloS one, vol. 11, no. 5, pp. e0155123 |
| سنة النشر: | 2016 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Camptothecin/analogs & derivatives, Camptothecin/pharmacology, Camptothecin/therapeutic use, Cell Line, Tumor, Chemotherapy, Adjuvant, Clinical Trials as Topic, Cohort Studies, Colonic Neoplasms/drug therapy, Colonic Neoplasms/genetics, Disease-Free Survival, Drug Evaluation, Preclinical, Fluorouracil/pharmacology, Fluorouracil/therapeutic use, Gene Expression Profiling, Gene Expression Regulation, Neoplastic/drug effects, Humans, Prognosis |
| الوصف: | This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. To test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. There was no statistically significant association between the irinotecan or SN-38 profiles and benefit from irinotecan. The 5-FU sensitivity profile showed a statistically significant association with relapse free survival (RFS) (hazard ratio (HR) = 0.54 (0.41-0.71), p<1e-05) and overall survival (HR = 0.47 (0.34-0.63), p<1e-06) in the PETACC-3 subpopulation. The effect of the 5-FU profile remained significant in a multivariable Cox Proportional Hazards model, adjusting for several relevant clinicopathological parameters. No statistically significant effect of the 5-FU profile was observed in the untreated cohort of 359 patients (relapse free survival, p = 0.671). The irinotecan predictor had no predictive value. The 5-FU predictor was prognostic in stage III patients in PETACC-3 but not in stage II patients with no adjuvant therapy. This suggests a potential predictive ability of the 5-FU sensitivity profile to identify colon cancer patients who may benefit from 5-FU, however, any biomarker predicting benefit for adjuvant 5-FU must be rigorously evaluated in independent cohorts. Given differences between the two study cohorts, the present results should be further validated. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27171152; info:eu-repo/semantics/altIdentifier/eissn/1932-6203; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_E521F016CAEB1; https://serval.unil.ch/notice/serval:BIB_E521F016CAEBTest; urn:issn:1932-6203; https://serval.unil.ch/resource/serval:BIB_E521F016CAEB.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_E521F016CAEB1Test |
| DOI: | 10.1371/journal.pone.0155123 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0155123Test https://serval.unil.ch/notice/serval:BIB_E521F016CAEBTest https://serval.unil.ch/resource/serval:BIB_E521F016CAEB.P001/REF.pdfTest http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_E521F016CAEB1Test |
| حقوق: | info:eu-repo/semantics/openAccess ; Copying allowed only for non-profit organizations ; https://serval.unil.ch/disclaimerTest |
| رقم الانضمام: | edsbas.6EC30DD6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0155123 |