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Abstract
Introduction/Background Ovarian cancer (OC), the most malignant gynecological tumor, exhibits diverse therapeutic responses. Patient-derived in vitro models for drug screening offer an individualized approach to overcome interpatient heterogeneity. Bypassing the limitations of xenografts and organoids, 3D bioprinting (3DP) offers high-throughput, high fidelity, and a drug screening timeline of 8 days, which is of clinical significance. We hereby reported the establishment of patient-derived 3DP-OC models with personalized drug sensitivity results.
Methodology Tumor specimens of newly diagnosed OC patients were collected at Peking Union Medical College Hospital (PUMCH) from 2022–07 to 2023–11, with informed consent and PUMCH ethics committee approval. Tumors were digested into cell suspensions and mixed with GelMA to form bioinks. 3DP-OC was fabricated by an extrusion-based bioprinter, and treated with a panel of chemo- and targeted therapy drugs in dose gradients at DIV 5(a). Cell viability was measured by CellTiter-Glo® assay for dose-response curves and IC50.
Results We have established 3DP-OC in 45 cases, including 38 high-grade serous ovarian cancer, 4 ovarian clear cell carcinoma, 1 ovarian sarcoma, 1 endometrioid carcinoma and 1 neuroendocrine tumor. The success rate is 100% with consistent viability during bioprinting and extended culture of up to 2 weeks(b). IHC and IF staining verified the comparable expression of OC markers and Ki-67 between 3DP-OC and tumor tissue(c-d). Interpatient heterogeneous response of drugs was observed in paclitaxel, carboplatin, cisplatin, doxorubicin, niraparib, olaparib, anlotinib and lenvatinib(e). Drug synergy of paclitaxel and carboplatin, first-line treatment of OC, were tested on 5 cases with disparate responses(f). One of which was clear cell carcinoma with frequent clinical resistance to platin-based therapy, urging a necessity of personalized therapy.
Conclusion We established 3DP-OC on 45 cases with exceptional efficiency. 3DP-OC demonstrated diverse drug responses, underlining its potential for precision medicine. Our ongoing research aims to correlate 3DP-OC drug responses with clinical outcomes.
Disclosures This work was supported by the CAMS Innovation Fund for Medical Sciences (2021-I2M-1–058), National High Level Hospital Clinical Research Funding (2022-PUMCH-045, 2022-PUMCH-B-034) and National Natural Science Foundation of China (32271470).
