Personalized screening in patient derived organoids for gastroenteropancreatic neuroendocrine tumors

Authors

• SD Forsythe
• S Yellapragda
• SG Andrews
• J del Rivero
• JM Hernandez
• N Nilubol
• JP Madigan
• SM Sadowski

Abstract

Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) are a rare subset of cancers which constitute a rising health burden. Development of new therapies suffers from bottlenecks including low patient accrual and poor understanding of tumor characteristics. Patient tumor organoids (PTOs) are a novel model capable of screening in an accurate, standardized, and high-throughput capacity. In this study, we developed PTOs from GEP-NENs to evaluate therapy responses. Tumors from patients undergoing clinically guided surgeries were dissociated into cell suspension. Cells were encapsulated into Matrigel and cultured into two groups. The first group was grown for 10 days, assessed for viability then treated with a panel of clinically approved therapies and experimental treatments. The second group was grown for long-term expansion and biobanking, followed by immunohistochemistry characterization to ensure tumor cell maintenance. From March 2023-November 2023, 1 patients provided 30 tumors for PTO development, including small intestine (n=5), pancreatic (n=8), and gastric (n=1) origins. Long-term culture (>3 passages) was successful for 23/30 (77%), with passage timing related to tumor grade. PTOs maintained immunohistochemical characteristics including neuroendocrine markers synaptophysin, chromogranin A, and ki67 proliferative index. Therapeutic screening demonstrated tumor grade dependent treatment efficacy and showing clinically dose relevant sensitivity towards small molecule inhibitor therapies. Testing of therapies recommended by cell line treatment panels suggested efficacy for proteosome inhibitors, MEK inhibitors, and topoisomerase inhibitors. Development of GEP-NEN PTOs is feasible for long term culture and standard of care therapy testing. Further study demonstrated the successful application of novel therapeutic options in PTO of patients with GEP-NENs.

Scientific Focus Area: Cancer Biology

This page was last updated on Tuesday, August 6, 2024