Development and validation of a functional ex vivo paclitaxel and eribulin sensitivity assay for breast cancer, the REMIT assay

Zofia M. Komar; Nicole S. Verkaik; Ahmed Dahmani; Elodie Montaudon; Roland Kanaar; Adriaan B. Houtsmuller; Agnes Jager; Elisabetta Marangoni; Dik C. van Gent

doi:10.1038/s41523-025-00734-x

Development and validation of a functional ex vivo paclitaxel and eribulin sensitivity assay for breast cancer, the REMIT assay

Zofia M. Komar, Nicole S. Verkaik, Ahmed Dahmani, Elodie Montaudon, Roland Kanaar, Adriaan B. Houtsmuller, Agnes Jager, Elisabetta Marangoni, Dik C. van Gent^*

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	17
Journal	npj Breast Cancer
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41523-025-00734-x
Publication status	Published - 17 Feb 2025

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Publisher Copyright: © The Author(s) 2025.

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title = "Development and validation of a functional ex vivo paclitaxel and eribulin sensitivity assay for breast cancer, the REMIT assay",

abstract = "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.",

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AU - Komar, Zofia M.

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AU - Dahmani, Ahmed

AU - Montaudon, Elodie

AU - Kanaar, Roland

AU - Houtsmuller, Adriaan B.

AU - Jager, Agnes

AU - Marangoni, Elisabetta

AU - van Gent, Dik C.

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AB - 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.

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Development and validation of a functional ex vivo paclitaxel and eribulin sensitivity assay for breast cancer, the REMIT assay

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