Establishment of novel patient-derived preclinical models for neuroendocrine tumors (B05)

Introduction: Neuroendocrine tumors (NETs) arise in different organs and are heterogeneous with limited treatment options. Preclinical models established from patient tumor specimens enable precision oncology by assessing the response to various drug treatments.

Aim(s): Herein, we aim to establish patient-derived organoids (PDOs) and xenografts (PDXs) for NETs.

Materials and methods: To establish PDOs, fresh surgical surplus NET tissue sample is disassociated in single-cell suspension, and the cells are seated in 384-well plates coated with extracellular matrix. We use non-toxic dyes and confocal imaging to follow the PDOs’ progression and morphological characteristics. To establish NET patient-derived xenograft ex-ovo (PDXovo) models, we engraft small tumor tissue fragments into the chorioallantoic membrane of chicken embryos. High-frequency ultrasound imaging was used to measure changes in tumor volume and vascularity.

Results: We established PDOs from various primary NETs and lymph node and liver metastasis with > 90% success. Our data show that PDOs from liver metastasis grow at a higher rate compared to the corresponding primary tumors and respond differently to various treatments. Moreover, we derived over 100 PDXovos from primary tumors and lymph node and liver metastases with > 80% take rate. Histologically, PDXovos preserve the cellular architecture found in the original NET sample. Using our robotic facility, we plan to use the NET-PDO platform to screen for FDA-approved drugs and subsequently validate using the NET-PDXovo models.

Conclusion: Overall, this study showed that we can derive NET preclinical models on a large scale reproducibly. Utilizing the dual approach of PDOs/PDXovo preclinical models will enable us to identify new potential treatments for patients with NETs.

Keywords: preclinical models, patient-derived organoids, patient-derived xenografts, drug screening