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@article{1311692,
author = {Jensen, Niels F. and Stenvang, Jjan and Beck, Mette K. and Hanáková, Barbora and Belling, Kirstine C. and Do, Khoa N. and Viuff, Birgitte and Nygard, Sune B. and Gupta, Ramneek and Rasmussen, Mads H. and Tarpgaard, Line S. and Hansen, Tine P. and Budinská, Eva and Pfeiffer, Per and Bosman, Fred and Tejpar, Sabine and Roth, Arnaud and Delorenzi, Mauro and Andersen, Claus L. and Rømer, Maria U. and Brünner, Nils and Moreira, José M.A.},
article_location = {Oxford},
article_number = {6},
doi = {http://dx.doi.org/10.1016/j.molonc.2015.02.008},
keywords = {Colorectal cancer; Oxaliplatin; Irinotecan; Resistance; Cell line models},
language = {eng},
issn = {1574-7891},
journal = {Molecular oncology},
title = {Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance},
volume = {9},
year = {2015}
}
TY - JOUR
ID - 1311692
AU - Jensen, Niels F. - Stenvang, Jjan - Beck, Mette K. - Hanáková, Barbora - Belling, Kirstine C. - Do, Khoa N. - Viuff, Birgitte - Nygard, Sune B. - Gupta, Ramneek - Rasmussen, Mads H. - Tarpgaard, Line S. - Hansen, Tine P. - Budinská, Eva - Pfeiffer, Per - Bosman, Fred - Tejpar, Sabine - Roth, Arnaud - Delorenzi, Mauro - Andersen, Claus L. - Rømer, Maria U. - Brünner, Nils - Moreira, José M.A.
PY - 2015
TI - Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance
JF - Molecular oncology
VL - 9
IS - 6
SP - 1169-1185
EP - 1169-1185
PB - Elsevier Science Inc.
SN - 15747891
KW - Colorectal cancer
KW - Oxaliplatin
KW - Irinotecan
KW - Resistance
KW - Cell line models
N2 - Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mechanisms associated with chemoresistance, and departing from three distinct CRC cell models, we generated a panel of human colorectal cancer cell lines with acquired resistance to either oxaliplatin or irinotecan. We characterized the resistant cell line variants with regards to their drug resistance profile and transcriptome, and matched our results with datasets generated from relevant clinical material to derive putative resistance biomarkers. We found that the chemoresistant cell line variants had distinctive irinotecan- or oxaliplatin-specific resistance profiles, with non-reciprocal cross-resistance. Furthermore, we could identify several new, as well as some previously described, drug resistance-associated genes for each resistant cell line variant. Each chemoresistant cell line variant acquired a unique set of changes that may represent distinct functional subtypes of chemotherapy resistance. In addition, and given the potential implications for selection of subsequent treatment, we also performed an exploratory analysis, in relevant patient cohorts, of the predictive value of each of the specific genes identified in our cellular models.
ER -
JENSEN, Niels F., Jjan STENVANG, Mette K. BECK, Barbora HANÁKOVÁ, Kirstine C. BELLING, Khoa N. DO, Birgitte VIUFF, Sune B. NYGARD, Ramneek GUPTA, Mads H. RASMUSSEN, Line S. TARPGAARD, Tine P. HANSEN, Eva BUDINSKÁ, Per PFEIFFER, Fred BOSMAN, Sabine TEJPAR, Arnaud ROTH, Mauro DELORENZI, Claus L. ANDERSEN, Maria U. RØMER, Nils BRÜNNER and José M.A. MOREIRA. Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance. \textit{Molecular oncology}. Oxford: Elsevier Science Inc., 2015, vol.~9, No~6, p.~1169-1185. ISSN~1574-7891. Available from: https://dx.doi.org/10.1016/j.molonc.2015.02.008.
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