Advancing neuroblastoma therapy
Neuroblastoma is an aggressive solid neuroendocrine tumour that emerges early on in childhood. It has a poor survival rate and accounts for 15 % of cancer-related deaths in children under the age of 15. Such tumours are often impenetrable to chemotherapy agents and as a result resistant to conventional treatments. The EU-funded NEUROBLASTOMA CHEMO (Chemotherapy of neuroblastoma) project aimed to improve these dismal statistics by designing pharmacological treatments with better penetrance to circumvent some of the resistance mechanisms. As a first step, scientists evaluated anticancer drug distribution in the intracellular, extracellular and vascular tumour compartments in patient-derived in vivo xenografts. They observed that the intra-tumour drug distribution of the active metabolite irinotecan was higher in relapse than in primary tumours. This suggested that treatment of chemoresistant tumours could improve by pharmaceutical methods that increase tumour penetrance. For this purpose, the consortium designed a new drug-delivery system based on biocompatible polymer nanofibres as carriers of irinotecan microcrystals. Deposition of this delivery system on the surgical bed following tumour resection surgery produced promising results in preclinical models of paediatric solid tumours. Active drug concentrations were detected locally thereby minimising tumour recurrence and minimal escape into the bloodstream was observed. Overall, the results of the NEUROBLASTOMA CHEMO study open up new avenues for the treatment of multidrug resistant neuroblastoma. The next step of the project is to bring this patented technology to the clinic and design a patient study.
Keywords
Neuroblastoma, chemotherapy, penetrance, drug-delivery system, irinotecan
