Organoids-on-a-chip for Colorectal Cancer and in Vitro Screening of Chemotherapeutic Drugs

Prospective Observation on the Accuracy of in Vitro Screening of Colorectal Cancer Chemotherapy Drugs Based on Organoids-on-a-chip

The individualized treatment of tumors has always been an urgent problem in clinical practice. Organoids-on-a-chip can reflect the heterogeneity of tumors and is a good model for in vitro anticancer drug screening. In this study, surgical specimens of patients with advanced colorectal cancer will be collected for organoid culture and organoids-on-a- chip. Use organoids-on-a-chip to screen tumor chemotherapy drugs, compare the results of patients' actual medication regimens, and study the guiding role of organoids in the formulation of precise tumor treatment plans. The investigators will compare the response of organoids to drugs in vitro with the patient's response to actual chemotherapy and targeted drugs and explore the feasibility and accuracy of organoids-on-a-chip based drug screening for advanced colorectal cancer. The project will establish a screening platform for chemotherapeutic drugs and targeted drugs based on colorectal cancer organoids to quickly and accurately formulate personalized treatment plans for clinical patients.

1. Establish and identify colorectal cancer organoid chip culture system: collect tumor tissues and normal tissues from patients with advanced colorectal cancer. Culture primary organoids, and organoids derived from normal mucosal tissues as controls. Validate tumor organoids and organoid chips by morphology (HE, immunohistochemical staining) and gene sequencing (target-seq) methods.
2. After each enrolled patient undergoes MDT discussion, chemotherapy is given to the patient according to the existing clinical guidelines and clinical pathways for colorectal cancer. Meanwhile, in vitro drug screening based on colorectal cancer organoid chips is conducted. Collect target gene sequencing results and common clinical medication plans. Local recurrence rate, disease progression-free survival rate and overall survival rate will be followed up for 2 years.
3. Compare the patient's response to the actual medication regimen and organoids in vitro drug screening based on organoids-on-a-chip, and evaluate the accuracy, specificity and sensitivity of organoids-on-a-chip for in vitro drug screening.

Inclusion Criteria:

1. Patients voluntarily participate the study and sign informed consent, with good compliance and follow-up;
2. Patients who can tolerate chemotherapy and targeted therapy, ECOG≤1 point;
3. Patients with advanced colorectal cancer diagnosed by pathology and imaging; 4. Neutrophil count ≥2.0×10^9/L, Platelet count ≥100×10^9/L, Hemoglobin ≥90g/L, Serum total bilirubin ≤ 1.5 times the upper limit of normal value, Alanine aminotransferase and Aspartate aminotransferase ≤ 1.5 times the upper limit of normal value, and Serum creatinine ≤ 1.5 times the upper limit of normal value.

Exclusion Criteria:

1. Patients who cannot obtain enough tissue for gene test and the organoids-on-a-chip culture;
2. Patients previously combined with other malignant tumors of other organs;
3. Patients who need emergency operation due to perforation and obstruction；
4. Patients who have active hepatitis, HIV (+) and other conditions that cannot tolerate chemotherapy;
5. Patients who have serious heart and lung diseases, vascular diseases, mental diseases or drug abuse.