Abstract

Cancer remains one of the leading causes of death in the 21^st century. Despite the latest advances in oncology, the majority of cancer patients lack tailored therapeutic approaches with lasting benefit.

Readily measuring the impact of anticancer compounds and their combinations is possible only on ex vivo assays. However, fresh primary cell cultures remain challenging to establish for testing ex vivo in a clinically relevant manner both in terms of time and biological relevance.

To this end, patient-derived organoids (PDOs) have been proposed as viable and efficient alternatives for ex vivo testing. PDOs show long-term expansion potential while retaining tumor histopathology as well as cancer gene mutations. However, the translation of PDOs to the industry for screening applications has so far been hampered by the lack of homogeneity and difficult handling and automatability, and cumbersome analyses of organoid culture in solid ECM drops. 

We set up an automated screening workflow using Gri3D^®, an innovative hydrogel-based ultra-dense U-bottom shaped microcavity array platform. On Gri3D^®, organoids are robustly generated in the microwells and are located in the same imaging plane, facilitating quantitative analyses in high content image-based phenotypic screens. Moreover, the pipetting port facilitates automation of cell seeding, media exchange and compound incubation with liquid-handlers, thus increasing assay reproducibility. We use a Live/Dead assay to assess drug and drug combination effects on PDOs. Using the SUN bioscience automated analysis platform, acquired images are processed and results are extracted in under one hour, reducing the time until a response is given to the clinics.

The data demonstrate on human pancreatic cancer organoids how amalgamation of anti-cancer drugs could enhance efficacy compared to mono-therapy approaches while reducing toxic side effects.