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

Molecular Oncology
Niels Frank JensenJosé M A Moreira

Abstract

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 im...Continue Reading

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Citations

Apr 1, 2016·Journal of Experimental & Clinical Cancer Research : CR·Niels Frank JensenYves Pommier
Sep 8, 2017·International Journal of Molecular Sciences·Dorte Lisbet NielsenBirgitte Martine Viuff
Jun 28, 2020·AAPS PharmSciTech·Laura CabezaConsolación Melguizo
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Nov 7, 2021·Journal of Experimental & Clinical Cancer Research : CR·Qingguo LiZiliang Wang

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