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Open AccessArticle

Prediction of Drug Efficacy in Colon Cancer Preclinical Models Using a Novel Ranking Method of Gene Expression

INSERM U1109, Microenvironmental Niche in Tumorigenesis and Targeted Therapy (MN3T Lab), University of Strasbourg, Labex Medalis, Fédération de Médecine Translationnelle, 67000 Strasbourg, France
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Author to whom correspondence should be addressed.
Current address: INSERM U1119, BMNST Lab, University of Strasbourg, Labex Medalis, Fédération de Médecine Translationnelle, 67000 Strasbourg, France.
Cancers 2020, 12(1), 149; https://doi.org/10.3390/cancers12010149
Received: 15 November 2019 / Revised: 31 December 2019 / Accepted: 6 January 2020 / Published: 8 January 2020
The presence of stromal cells in tumors is altering the significance of molecular profiling when using standard methods of gene expression quantification. We developed a novel normalization method to rank target gene expression in tumor samples by comparisons with reference samples representing the different cell types found in a tumor. The score for each target gene obtained after normalization, is aimed to be predictive of targeted therapies efficiency. We performed this qPCR analysis on human colorectal cancers to demonstrate the importance of reference samples to obtain accurate data and on a collection of patient-derived xenografted (PDX) colon tumors treated with Cetuximab (anti-EGFR) to demonstrate that the calculated EGFR score is predictive of Cetuximab efficacy. Interestingly, the score allowed to select an efficient treatment in a PDX model refractory to standard of care. This method is opening a novel way to predict targeted therapy efficiency which could be extended to several tumor types, and to unlimited target genes. View Full-Text
Keywords: gene expression; drug efficacy; targeted therapy selection; molecular profiling gene expression; drug efficacy; targeted therapy selection; molecular profiling
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MDPI and ACS Style

Fritz, J.; Lefebvre, O.; Fernandez, A.; Schmidt, J.; Bagnard, D. Prediction of Drug Efficacy in Colon Cancer Preclinical Models Using a Novel Ranking Method of Gene Expression. Cancers 2020, 12, 149.

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