Their findings have been published in Cell Reports. PDOs, known as experimental avatars, can predict a patient's drug response and hold great promise for personalizing cancer treatments. However, their potential as a preclinical screening platform for drug discovery and therapy development remains largely untapped.

To overcome the issue of dormant drug-resistant cells being metabolically inactive, Snippert and colleagues designed a novel microscopy-based drug screen that accurately distinguishes dead from living organoids. Using Oncode’s drug repurposing library, they tested 414 potential anti-cancer drugs for their ability to eliminate these resistant cells. A majority of the most effective drugs were found to be microtubule-targeting agents (MTAs), which are already commonly used in clinical oncology, such as taxanes and vinca-alkaloids.

One of these drugs, vinorelbine, demonstrated consistent effectiveness across 25 different colon cancer PDOs, regardless of RAS mutational status. The combination of vinorelbine with EGFR/MEK inhibition induced apoptosis at all stages of the cell cycle and displayed promising anti-tumor activity in vivo.

Hugo Snippert says: “Using the infrastructure and financial support from Oncode via the Clinical Proof of Concept fund, we teamed up with Jeanine Roodhart (UMCU) who leads a clinical trial to test the beneficial effect of vinorelbine, the most promising MTA in our study, in patients with RAS mutant metastatic colon cancers that receive targeted therapy against the RAS signaling pathway. We hope that our anticipation is justified that additional disturbance of the MT network will suffocate the drug-tolerant cells.”