Breast cancer therapy response | Mimetas

Breast cancer therapy response

Breast cancer therapy response

Background

Breast cancer is the most common invasive cancer among women. Currently, there are only a few models used for therapy selection, and they are often poor predictors of therapeutic response or take months to set up and assay. In this report, we introduce a microfluidic OrganoPlate® platform for extracellular matrix (ECM) embedded tumor culture under perfusion as an initial study designed to investigate the feasibility of adapting this technology for therapy selection.

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Methods and results

Cisplatin exposure of PDX-derived human breast cancer cells in 3D microfluidic culture

The triple negative breast cancer cell lines MDA-MB-453, MDA-MB-231 and HCC1937 were selected based on their different BRCA1 and P53 status, and were seeded in the platform. We evaluate seeding densities, ECM composition (Matrigel®, BME2rgf, collagen I) and biomechanical (perfusion vs static) conditions. We then exposed the cells to a series of anti-cancer drugs (paclitaxel, olaparib, cisplatin) and compared their responses to those in 2D cultures. Finally, we generated cisplatin dose responses in 3D cultures of breast cancer cells derived from 2 PDX models.

The microfluidic platform allows the simultaneous culture of 96 perfused micro tissues, using limited amounts of material, enabling drug screening of patient-derived material. 3D cell culture viability is improved by constant perfusion of the medium. Furthermore, the drug response of these triple negative breast cancer cells was attenuated by culture in 3D and differed from that observed in 2D substrates.

Figure: Cisplatin exposure of PDX-derived human breast cancer cells in 3D microfluidic culture. Human cancer cells from two different breast cancer PDX avatars were isolated and seeded in 3D in the OrganoPlate® 1 day prior to 48 h cisplatin exposure to 2 different PDX tissues.

Conclusions and future prospects

Outlook: Work flow for Patient derived xenograft (PDX) vs cancer-on-a-chip drug screening.

We have investigated the use of a high-throughput organ-on-a-chip platform to select therapies. Our results have raised the possibility to use this technology in personalized medicine to support selection of appropriate drugs and to predict response to therapy in a real-time fashion.

Figure: Workflow for Patient-Derived Xenograft (PDX) vs cancer-on-a-chip drug screening. Compared to PDX drug screening, the compact
OrganoPlate® platform is expected to reduce assay time and space, and increase the throughput of screened compounds, leading to improvements in cancer treatment planning and personalized medicine for individual patients