Zofia M Komar, Nicole S Verkaik, Ahmed Dahmani, Elodie Montaudon, Roland Kanaar, Adriaan B Houtsmuller, Agnes Jager, Elisabetta Marangoni, Dik C van Gent
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Development and validation of a functional ex vivo paclitaxel and eribulin sensitivity assay for breast cancer, the REMIT assay.
Breast cancer is the most common cancer amongst women worldwide, however clinically validated chemotherapy response biomarkers that can accurately predict treatment response in patients are largely lacking. Therefore, in this study, functional paclitaxel and eribulin ex vivo sensitivity assays were developed. Patient derived xenograft (PDX) models were used to compare the ex vivo predicted treatment outcome with the sensitivity of mice in vivo. We validated the previously developed sensitivity assay for paclitaxel, which is based on the ratio between replicating (EdU) and mitotic (phospho-Histone H3; pH3) cells as a proxy for blocked mitosis. The assay showed 90% correlation between the ex vivo and in vivo response to paclitaxel treatment in the PDX models. We propose the term REMIT (REplication MITosis) assay and show that it is also a suitable test to predict eribulin sensitivity. The reproducibility of the REMIT assay for paclitaxel and eribulin was determined to be 80% and 83%, respectively. These results justify further clinical validation of the REMIT assay in breast cancer patients.
期刊介绍：
npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.
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