Personalizing colorectal Cancer treatment: Chemotherapy drug testing with patient-derived tumor cell clusters

Abstract

Background

Due to the heterogeneity of colorectal cancer (CRC), models that can predict the chemotherapy response are needed to facilitate personalized treatment.

Aim

To construct patient-derived tumor-like cell cluster (PTC) models in vitro drug sensitivity screening for CRC personalized chemotherapy.

Methods

We collected 140 CRC tissues via surgical resection in three Chinese hospitals and establish PTC models which is highly similar to the original tumor tissue. The sensitivity to various chemotherapy drugs was assessed in these PTC models. We recorded the PTC model cultivation process and patients' clinical data and assessed the concordance between in vitro drug sensitivity and clinical outcomes.

Results

PTC models were successfully established from 124 specimens, with a success rate of 88.6 %. The average culture time was 3.02 ± 1.56 days, and the median time to obtain drug sensitivity results was 11 days (10–13 days). Drug sensitivity testing revealed that the PTC models had variable responses to different chemotherapy regimens, with some patients showing unexpected sensitivity to regimens not typically considered first-line treatments. The median follow-up time for all patients was 19 months, and there was no significant difference in disease-free survival (DFS) between patients whose actual responses to clinical treatment regimens were consistent or inconsistent with the PTC model predictions.

Conclusion

The PTC model for drug sensitivity testing has advantages of high success rate and rapid drug screening time. This study provides a promising tool for personalized chemotherapy sensitivity screening in patients with CRC and, after further clinical trials, may guide clinical treatment decision making.