J 2015

Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance

JENSEN, Niels F., Jjan STENVANG, Mette K. BECK, Barbora HANÁKOVÁ, Kirstine C. BELLING et. al.

Základní údaje

Originální název

Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance

Autoři

JENSEN, Niels F. (208 Dánsko), Jjan STENVANG (208 Dánsko), Mette K. BECK (208 Dánsko), Barbora HANÁKOVÁ (203 Česká republika, domácí), Kirstine C. BELLING (208 Dánsko), Khoa N. DO (208 Dánsko), Birgitte VIUFF (208 Dánsko), Sune B. NYGARD (208 Dánsko), Ramneek GUPTA (208 Dánsko), Mads H. RASMUSSEN (208 Dánsko), Line S. TARPGAARD (208 Dánsko), Tine P. HANSEN (208 Dánsko), Eva BUDINSKÁ (703 Slovensko, garant, domácí), Per PFEIFFER (208 Dánsko), Fred BOSMAN (756 Švýcarsko), Sabine TEJPAR (56 Belgie), Arnaud ROTH (756 Švýcarsko), Mauro DELORENZI (756 Švýcarsko), Claus L. ANDERSEN (208 Dánsko), Maria U. RØMER (208 Dánsko), Nils BRÜNNER (208 Dánsko) a José M.A. MOREIRA (208 Dánsko)

Vydání

Molecular oncology, Oxford, Elsevier Science Inc. 2015, 1574-7891

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 5.367

Kód RIV

RIV/00216224:14110/15:00083911

Organizační jednotka

Lékařská fakulta

UT WoS

000356128200011

Klíčová slova anglicky

Colorectal cancer; Oxaliplatin; Irinotecan; Resistance; Cell line models

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 21. 9. 2015 11:56, Soňa Böhmová

Anotace

V originále

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.