Stem Cell-Based Model Mimics Early Stages of Neuroblastoma Formation

Researchers from the University of Sheffield have created a human embryonic stem cell (hESC)-based model to investigate the origins of neuroblastoma, a cancer primarily affecting babies and young children. Until now, studying genetic changes and their role in neuroblastoma initiation has been challenging due to the lack of suitable laboratory methods. The new model developed replicates the emergence of early neuroblastoma cancer-like cells, giving an insight into the genetic pathway of the disease.

The study, published in Nature Communications, sheds light on the intricate genetic pathways that initiate neuroblastoma. The research team found that specific mutations in chromosomes 17 and 1, combined with overactivation of the MYCN gene, play a pivotal role in the development of aggressive neuroblastoma tumors.

Childhood cancer is often diagnosed and detected late, leaving researchers with little idea of the conditions that led to tumor initiation, which occurs very early during fetal development. To understand tumor initiation, models that recreate the conditions leading to the appearance of a tumor are vital.

In an interdisciplinary effort, the researchers found a way to use human stem cells to grow trunk neural crest cells in a petri dish. These cells carried genetic changes often seen in aggressive neuroblastoma tumors. Using genomics analysis and advanced imaging techniques, the researchers found that the altered cells started behaving like cancer cells and looked very similar to the neuroblastoma cells found in sick children.

The findings offer new hope for the creation of tailored treatments that specifically target the cancer while minimizing the adverse effects experienced by patients from existing therapies.

"Our stem cell-based model mimics the early stages of aggressive neuroblastoma formation, providing invaluable insights into the genetic drivers of this devastating childhood cancer," said Anestis Tsakiridis, the study's lead author. "By recreating the conditions that lead to tumor initiation, we will be able to understand better the mechanisms underpinning this process and thus design improved treatment strategies in the longer term."