Abstract 416P
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 in 41 patients.
Methods
Tumor specimens of newly diagnosed OC patients were collected at Peking Union Medical College Hospital (PUMCH) from 2022-07 to 2023-07, with informed consent and PUMCH ethics committee approval. Tumors were digested into cell suspensions and mixed with GelMA to a final concentration of 1×107cell/mL. 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. Cell viability was measured by CellTiter-Glo® assay after 72 hours for dose-response curves and IC50.
Results
We have established 3DP-OC in 41 cases, including 34 high-grade serous ovarian cancer, 4 ovarian clear cell carcinoma, 1 ovarian sarcoma, 1 endometrioid carcinoma and 1 neuroendocrine tumor. The success rate was 100% with consistent viability during bioprinting and extended culture of up to 2 weeks. IHC and IF staining verified the comparable expression of OC markers and Ki-67 between 3DP-OC and tumor tissue. Interpatient heterogeneous response of drugs was observed in paclitaxel, carboplatin, cisplatin, doxorubicin, niraparib, olaparib, anlotinib and lenvatinib. Drug synergy of paclitaxel and carboplatin, first-line treatment of OC, were tested on 5 cases with disparate responses. One of which was clear cell carcinoma with frequent clinical resistance to platin-based therapy, urging a necessity of personalized therapy.
Conclusions
We established 3DP-OC on 41 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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
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).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
561P - Mechanisms of osimertinib resistance using circulating tumor DNA analyses for EGFR-mutated non-small cell lung cancer, results from ELUCIDATOR: A prospective observational multicenter study
Presenter: Daijiro Harada
Session: Poster Display
Resources:
Abstract
562P - First-line (1L) osimertinib (osi) ± platinum-pemetrexed in patients (pts) with EGFRm advanced NSCLC: FLAURA2 China cohort
Presenter: Yan Yu
Session: Poster Display
Resources:
Abstract
563P - Real-world effectiveness and safety of first-line osimertinib for EGFR-mutated advanced NSCLC in China (FLOURISH study)
Presenter: Jianya Zhou
Session: Poster Display
Resources:
Abstract
564P - Co-occurring EGFR p.E709X mutation affects the treatment response to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients with advanced NSCLC
Presenter: Wen Feng Fang
Session: Poster Display
Resources:
Abstract
565P - Genome-guided targeted therapy combination improves survival in patients with advanced EGFR mutation positive NSCLC failing osimertinib
Presenter: Molly Li
Session: Poster Display
Resources:
Abstract
566P - Safety of tepotinib + osimertinib in EGFR-mutant NSCLC with MET amplification after first-line osimertinib
Presenter: Chong Kin Liam
Session: Poster Display
Resources:
Abstract
567P - Furmonertinib in combination with bevacizumab and intrathecal chemotherapy as later-line re-challenge treatment in EGFR –mutated NSCLC patients with leptomeningeal metastasis after third-generation EGFR-TKIs treatment failure
Presenter: Fang Cun
Session: Poster Display
Resources:
Abstract
568P - First-line (1L) osimertinib + platinum-pemetrexed in EGFR-mutated (EGFRm) advanced NSCLC: Updated FLAURA2 safety run-in (SRI) results
Presenter: David Planchard
Session: Poster Display
Resources:
Abstract
569P - Whole-transcriptome sequencing of transformed small-cell lung cancer from EGFR-mutated lung adenocarcinoma reveals LUAD–like and SCLC–like subsets
Presenter: Chan-Yuan Zhang
Session: Poster Display
Resources:
Abstract
570P - First-line osimertinib for patients with advanced NSCLC harboring EGFR mutations: A real-world study
Presenter: Wenxiang Ji
Session: Poster Display
Resources:
Abstract