Abstract

Cancer-on-Chip Assay for Chemotherapy Sensitivity of Breast Cancer Tissue

Dik van Gent, Associate Professor, Erasmus Medical Center

Breast Cancer (BrC) response to chemotherapy is variable and biomarkers are not sufficient to correctly anticipate therapy response. Therefore, we aimed to develop an ex vivo assay to predict chemotherapy response in BrC patients, using a novel microfluidic platform. Patient-Derived Xenograft (PDX) tumors with known in vivo chemotherapy sensitivity or surgical BC samples were sliced and cultured in 6-wells plates (referred to as ex vivo culture), or in a Cancer-on-Chip (CoC) platform (BI/OND). Tissue slices were treated with the chemotherapeutic (e.g. cisplatin or paclitaxel) under both culture conditions. Tissue slices were Formalin-Fixed Paraffin-Embedded (FFPE) and 4 µm tissue sections were immunostained for proliferation, mitosis and/or apoptosis. Alternatively, a whole-mount immunostaining was performed to compare the 3D architecture of a fixed tissue slice with and without treatment. To observe cells over time a time-lapse experiment was done using Hoechst staining. The experimental setup allows assessment of the sensitivity of the PDX tumors by determining cellular proliferation, apoptosis and/or the ratio between mitotic and S-phase cells, depending on the chemotherapeutic used. The chemotherapeutics treatments yielded a better dose-response curve under the CoC culture conditions than the ex vivo method. Furthermore, CoC culture allowed longer incubation times without loss of viability (more than 14 days compared to 7 days).