1569P - The CODRP model for predicting drug sensitivity in patient-derived 3D gastric cancer cells

Background

Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. This study proposes a multi-factor analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test for gastric cancer patients.

Methods

Primary cells were isolated from surgical tissues from 143 gastric cancer (GC) patients and mixed with matrigel to make patient derived 3D cultured cells. Due to small number of patient’s cells, we used 384 pillar plate (MBD, Korea) for high throughput screening. 1.5ul spots dispensed on pillar and, the cells were stabilized in a culture medium optimized for GC cells for 3days and the drug response was observed for 7days. 3D cell morphology was scanned after calcein staining and cell viability was quantified using ATP assay. The primary characteristics of GC 3D cultured cells were confirmed by IHC. The drug responses were calculated by a sigmoidal dose response curve and compared to clinical case report form.

Results

Evaluation of drug response was established for various drugs in 143 patients and success rate was 71%. We analyzed drug response through CODRP analysis method using multi-factor (cell growth rate, TNM stage, AUC). In clinic, 56 patients were treated by oxaliplatin after surgery, the CODRP index about oxaliplatin compared with clinical response. Although the clinical recurrence rate was low due to the 1 year follow up, the early recurrence rate by CODRP analysis in the resistant group was 10%p higher than AUC analysis, while there was almost no difference in the sensitive group. When we analyze the 1-year recurrence-free survival rate in the CODRP model, the sensitive group showed 78% survival, while the resistant group showed 38.2% survival. Therefore, there was a significant difference in 1 year recurrence-free survival rate based on the CODRP model.

Conclusions

This study proposes a novel drug sensitivity prediction model using patient derived 3D cultured cells. In 56 gastric cancer patients, CODRP models based on the drug sensitivity AUC, growth rate, and cancer stage successfully predict clinical response of patient’s drug treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

MBD.

Disclosure

All authors have declared no conflicts of interest.