Application of tumoroids derived from advanced colorectal cancer patients to predict individual response to chemotherapy

Abstract

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.

Keywords:

• Tumoroids
• patient-derived organoids
• living biobank
• advanced colorectal cancer
• chemotherapy
• personalized medicine program

Authors' contributions

Peng-Fei Qiao designed the experiments. Hao-Gang Zhang, Xiao-Long Zao and Lei Yao performed the experiments. Lei Yao and Fu-Jing Wang analyzed the data and Peng-Fei Qiao and Xiao-Fei Pan wrote the manuscript. All authors approved the manuscript and agreed to be accountable for all aspects of the research in ensuring that the questions related to accuracy or integrity of any part of the work are appropriately investigated and resolved.

Data availability statement

The data presented in this study are available in the manuscript and Supplementary Materials. Any further information is available from the authors.

Disclosure statement

No potential conflict of interest was reported by the authors.

Informed consent statement

Informed consent was waived by the Institutional Review Board (see above).

Institutional review board statement

All patients provided written informed consent according to our institutional guidelines, and the study protocol was approved by the Institutional Research Ethics Committee of Harbin Medical University (KY2020-122).

Additional information

Funding

The present study was supported by Guanghua Funds For Medicine and Sociology Development Research (YX20210615#0054).