Authors

Discussion

Colorectal cancer (CRC) is the third leading cause of cancer and cancer-related death. A large fraction of the CRC patients diagnosed with de novo metastatic disease do not benefit from the standard of care but still experience substantial side effects. Therefore, there is the urgency for a new model to predict clinical response. Patient-derived organoids (PDOs or HUB Organoids^TM) are directly established from patient tissue, faithfully recapitulate patient disease and are proving to be a major breakthrough in pre-clinical models. Although PDOs greatly bridge the gap between the lab and the clinic and effectively bring a “patient in the lab”, patient benefits could be maximized when decreasing the turnaround time between patient diagnosis and obtaining PDO test results.

In the current study we aimed to 1) validate the predictive value of PDOs in the stratification of metastatic CRC (mCRC) patients for treatment with chemotherapeutic agents and 2) reduce diagnostic turnaround times. First, we implemented the logistics for acquisition of patient material for the study and optimized the procedure to establish PDOs from small needle biopsies of mCRC tissues. In collaboration with UMCU, PDO sensitivity towards the chemotherapeutic agent fluorouracil (5-FU) was evaluated by performing viability screening. Sensitive patients that showed long progression-free survival (PFS) or reduction in metastatic lesion size were very well represented by corresponding PDOs that demonstrated a small area under the curve (AUC) or low growth rate at maximum concentration (GRmax). In collaboration with Yamaha Motors using the Yamaha CELL HANDLER^TM to automatic and accurately pick-and-place organoids, low organoid numbers could be seeded automatically and with high accuracy. This would significantly decrease the number of organoids needed for drug screening thereby reducing the diagnostic turnaround time.