Patient-derived 3D bioprinting pan-cancer drug screening platform for personalized medicine.

e15088 Background: Patient-derived tumor model offers an individualized approach to overcome interpatient heterogeneity in cancer therapy. 3D bioprinting (3DB) enables construction of in vitro model with high-throughput, high-fidelity, and high efficacy. We hereby report a pipeline of establishing pan-cancer patient-derived 3DB (PT-3DB) models with personalized drug sensitivity results in 148 patients from multiple medical centers. Methods: Tumor tissues of 148 patients were collected with informed consent at 4 medical centers in Beijing, Hangzhou and Ningbo from 2022-12 to 2023-12. Tumors were digested into cell suspension and mixed with GelMA, and PT-3DB was fabricated by extrusion-based bioprinter. A panel of chemotherapies and targeted therapies was selected based on first-line treatment of corresponding cancer type. PT-3DB was treated with drugs in dose gradient at DIV 5. Cell viability was measured by ATP quantification at DIV 8 and dose-response curve and IC 50 of each drug was calculated. Results: We have established PT-3DB in 148 patients with success rate of > 95% and turnaround time of only 8 days. 137 were surgically resected samples and 11 were biopsy samples. Cancer types included ovarian cancer (OC, n = 52), colorectal cancer (CRC, n = 51), hepatobiliary cancer (HBC, n = 17), breast cancer (BC, n = 10), high-grade glioma (HGG, n = 10), cervical cancer (CC, n = 4), pancreatic cancer (PC, n = 2), and gastric cancer (GC, n = 2). A total of 27 drugs were screened, of which 15 were chemotherapies and 12 were targeted therapies. The median number of drugs tested for each patient was 5 (4-6) (Q25-Q75). Significant interpatient heterogeneous drug response was observed within each cancer type and between tumors with the same treatment regime. Representative data were presented in the attached table. Conclusions: We have successfully constructed pan-cancer PT-3DB platform for personalized drug screening in 148 cases, with outstanding stability across multiple centers. The timeline of 8 days preceded pathological diagnosis, which is the earliest start of systematic treatment, underscoring its high translational potential. PT-3DB has demonstrated interpatient heterogeneous response to systematic treatment, providing a strong foundation for precision medicine. Our ongoing research aims to correlate PT-3DB drug responses with clinical outcomes. Table: see text