Abstract
BACKGROUND: Colorectal cancer (CRC) is among the most common malignant tumors. Chemotherapy remains central to CRC management, yet many patients still fail to derive optimal benefit. Patient-derived tumor-like cell clusters (PTCs), a preclinical three-dimensional tumor model containing primary epithelial cells, fibroblasts, and immune cells, can more accurately predict drug efficacy because they closely resemble the original tumor tissue. AIM: To evaluate the feasibility of using PTCs to guide personalized chemotherapy for patients with CRC. METHODS: Fresh tumor tissues from 54 patients with resectable CRC were used to establish PTCs. Culture duration, diameter, and morphology were monitored. Hematoxylin-eosin staining was performed to assess PTC morphology. Drug sensitivity was evaluated through the PTC drug assay. RESULTS: PTCs exhibited inter- and intrapatient variability in growth rate, diameter, and morphology. Comparable proportions of PTCs showed strong or effective inhibition in response to FOLFOX and FOLFIRI. FOLFOXIRI demonstrated robust antitumor activity in 97% of PTC models. However, responses to FOLFOX and FOLFIRI varied considerably among individuals. FOLFOXIRI showed cell-killing activity similar to FOLFOX or FOLFIRI. CONCLUSION: Accounting for patient's pathological and clinical characteristics, PTC-based drug-sensitivity testing can help accurately identify effective agents for CRC in vitro. This novel preclinical platform may reduce unnecessary chemotherapy and support precision oncology.