Abstract

Precision medicine for cancer patients promises the tailoring of targeted therapies to specific genetic alterations. Currently, alterations in 43 oncogenes can be targeted based on Level 1 clinical evidence. Still, the majority of cancer patients lack efficient targeted therapy options with lasting benefit.

Ex vivo assays, such as tumor tissue explants, hold the promise to directly measure the impact of anticancer compounds and their combinations. A significant challenge for ex vivo drug testing lies in the efficient establishment of fresh primary cell cultures for testing, within clinically actionable timeframe, and in the available tumor volume.

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.

We have shown how homogenous reproducible PDOs based on Gri3D^® hydrogel microwell arrays could be generated for high-throughput drug testing of single and combination therapies.

Here we demonstrate on human pancreatic cancer organoids how amalgamation of anti-cancer drugs could enhance efficacy compared to mono-therapy approaches. By targeting pathways in a characteristically synergistic or an additive manner, a lower therapeutic dosage of each individual drug is required, potentially also reducing toxic side effects.