RNA-seq of subcutaneous patient-derived neuroblastoma xenografts (LU-NB-1) - Comparison of Prochlorperazine + Pitavastatin (PCZ+PIT) combination alone to one combined with standard-of-care COJEC protocol (PCZ+PIT+COJEC)
Neuroblastoma (NB) is a pediatric cancer characterized by significant heterogeneity and poor prognosis, specially in high-risk cases with MYCN amplification. Understanding the molecular response of neuroblastoma to different treatments can provide insights into potential therapeutic strategies. The aim of this experiment as to asses in vivo response of combination of Prochlorperazine and Pitavastatin alone or along standard of care chemotherapy COJEC. Neuroblastoma in vivo model was obtained via subcutaneous injection of human high-risk, MYCN-amplified neuroblastoma organoids in NSG mice (PDX, LU-NB-1). When tumors reached 200-300 mm3, mice were randomized into treatment groups: control (n=7), PCZ + PIT combination (n=7), and PCZ + PIT combination + COJEC (n=6).  PCZ + PIT (total volume 50 µl; 5 mg/kg of each drug) was administered i.t. daily five times per week. COJEC treatment was given i.p. and consisted of five different chemotherapies distributed in cycles over one week; Day 1 – cisplatin (1mg/kg) + vincristine (0,25mg/kg), Day 3 – etoposide (4mg/kg) + cyclophosphamide (75mg/kg), Day 5 – carboplatin (25mg/kg). All COJEC drugs were dissolved in saline and combination treatment was suspended in vehicle consisting of 2.5% DMSO, 2.5% Tween 80, 40% PEG, 55% PBS solution. Control mice were treated with i.t. injections of the vehicle used for PCZ+PIT and i.p injections of saline. Treatment was administered for 10 days, after which mice were euthanized, tumor pieces were collected snap-frozen. Mouse weights and tumor volumes were measured three times per week throughout the study. RNA was extracted from snap-frozen tumor pieces and RNA sequencing was conducted.