Live imaging of cancer therapy responses in human breast cancer

Fluorescent protein biomarker reporters in 3D patient-derived cancer models for imaging-based drug screening

The project will establish human relevant breast cancer test systems that will be applied in imaging-based anticancer drug screens. These models will include fluorescent biomarkers that can quantify biological pathways that are critical in cancer progression and drug responses. To accomplish this Leiden University will join forces with OcellO B.V. that will apply these new technologies for anticancer drug discovery.

1 in 8 women will develop breast cancer of which about thirty percent will die due to anticancer therapy resistance. There is an urgent need to discover improved anticancer drugs that can overcome a drug resistant phenotype. High throughput screening of large candidate drug libraries requires integration of both human relevant breast cancer models as well as biomarkers that are representative for cancer progression and drug sensitivity.

The innovative approach in this project is to integrate fluorescent protein biomarkers in human patient-derived breast cancer spheroids through state-of-the-art genetic engineering. Integration of these novel fluorescent biomarker breast cancer models in imaging-based screening setups will allow improved screening and selection of relevant candidate drug leads. The approach will lead to a better selection of candidate drugs that may be further developed for the improved treatment of breast cancer.

At the end of the project a panel of fluorescent reporter human breast cancer models will have been established as well as the strategies for the application of these innovative test systems for drug discovery campaigns. The technology will be implemented within OcellO B.V. to screen for the future relevant anticancer drugs and impact on the future treatment of breast cancer.

Summary
Thirty percent of breast cancer patients die to therapy resistant metastatic disease. There is a need for patient-relevant in vitro test systems to screen for candidate anticancer drugs. Current phenotypic screens reflect cell proliferation and cell survival that lack biomarkers of hallmarks of cancer. To increase the value of anticancer drug screens multiparametric phenotypic imaging-based screening will advance the selection of relevant candidates. The project will establish fluorescent biomarker-based test systems for improved imaging-based phenotypic anticancer drug screening strategies.
Technology Readiness Level (TRL)
3 - 5
Time period
24 months
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