Three-Dimensional Ex Vivo Culture for Drug Responses of Patient-Derived Gastric Cancer Tissue

Abstract

Gastric cancer (GC) is one of the most common malignancies with high mortality and substantial morbidity. Although the traditional treatment strategies for GC revolve around surgery, radiotherapy, and chemotherapy, none have been able to optimally treat most affected patients. To improve clinical outcomes and overcome potential GC resistance, we established a three-dimensional (3D) culturing platform that accurately predicts drug responses in a time- and cost-effective manner. We collected tumor tissues from patients following surgeries and cultured them for 3 days using our protocol. We first evaluated cell proliferation, viability, and apoptosis using the following markers: Ki67 and cleaved caspase 3 (Cas3). We demonstrated that cell viability was maintained for 72 h in culture and that the tumor microenvironments and vascular integrities of the tissues were intact throughout the culture period. We then administered chemotherapeutics to assess drug responses and found differential sensitivity across different patient-derived tissues, enabling us to determine individualized medication plans. Overall, our study validated this rapid, cost-effective, scalable, and reproducible protocol for GC tissue culture that can be employed for drug response assessments. Our 3D culture platform paves a new way for personalized medication in GC and other tumors and can greatly impact future oncological research.

Promising preclinical patient-derived organoid (PDO) and xenograft (PDX) models in upper gastrointestinal cancers: progress and challenges

“…PDOs of GC could be cultured from both tissue specimens and malignant ascites (Table 4) [40][41][42][43]. Gao et al developed 15 GC PDOs from 5 patients and identified similar KRAS alterations and drug sensitivity in primary tumours and paired organoids [41].…”

Cancer Stem Cells and the Tumor Microenvironment in Gastric Cancer

“…In addition, 3D culture systems can simulate the TME of CSCs by controlling the mechanical properties of materials and then effectively isolate CSCs. Recently, increasing studies have also used 3D culture systems to isolate and culture GCSCs (26)(27)(28)(29)(30).…”

A novel 3D pillar/well array platform using patient-derived head and neck tumor to predict the individual radioresponse

“…Also, with the advancement of bioengineering techniques and microfluidics, the 3D culture method of PDCs has the advantages of being easily reproducible and applicable to a high-throughput platform while maintaining the diversity of patient-native cancer tissues [ 11 , 12 ]. Thus, it is widely applied to research on cancer mechanisms and responsiveness to various anticancer treatments [13] , [14] , [15] , [16] . However, most previous studies regarding response to RT have been performed using tumor tissues stored in a biobank or grown in mice (PDX, patient-derived xenograft).…”