Biofabrication of pheochromocytoma and paraganglioma tumor organoids and assessment of response to systemic therapy

Abstract

Abstract Introduction Pheochromocytoma (PCC) and paraganglioma (PG) research is limited due to rarity of disease. We utilized patient-derived tumor organoids (PTOs) to explore personalized treatment options for these patients. Tumors were obtained from patients with PCC and PG who underwent operative resection and processed to biofabricate PTOs utilizing a collagen-based hydrogel. Blood was also obtained from patients to generate immune-enhanced PTOs (iPTOs). Organoids underwent treatment with chemotherapy, immunotherapy, or tyrosine kinase inhibitors. Cell viability was determined using multiple assays. Significant treatments demonstrated viability < 50% and p < 0.05 compared to controls. Twelve PCC and 4 PG tumors were obtained from December 2020 – May 2023. Viable PTOs were generated in 15/16 (93.8%) tumors for drug studies. Sunitinib (10 µM) demonstrated significant treatment efficacy in 9/14 PTOs (64.3%) with average post-treatment viability of 28%. A commonly utilized clinical regimen of cyclophosphamide, vincristine, doxorubicin and dacarbazine (10 µM) demonstrated significant treatment effect in 3/7 treated PTOs (42.9%) with average post-treatment viability of 25.5%. Only 1/13 iPTOs (7.7%) demonstrated sensitivity to Ipilimumab/Nivolumab. Cultured PTOs produced measurable norepinephrine on ELISA. PTOs are a feasible platform to study PCC and PG and their response to systemic treatments on a personalized level.